Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses"’ Version 1.0

Supplementary Text Manuscript Appendix "‘Systems vaccinology for a live attenuated tularemia vaccine reveals unique transcriptional signatures that predict humoral and cellular immune responses"’ Version 1.0

December 23, 2019

Table of Contents

1 Introduction 8

2 Supplemental methods 8 2.1 Study Design ...... 8 2.2 Microarray experiment ...... 8 2.3 Cell mediated immunity experiments ...... 9 2.4 Microarray data preprocessing ...... 10 2.5 Differential gene analysis ...... 11 2.6 Determination of robust gene clusters ...... 11 2.7 Gene set enrichment analysis ...... 11 2.8 Regularized logistic regression analysis ...... 12 2.9 Regularized canonical correlation analysis ...... 13 2.10 Comparisons with viral vaccine microarray studies ...... 14 2.11 Cell mediated immunity analysis ...... 15

3 Supplemental results 15

4 References 84

1 List of Tables

Table 1 Descriptive summary statistics of percent monocyte cells of live PBMCs fold change from baseline by treatment...... 16 Table 2 Descriptive summary statistics of percent monocyte cells (CD16+) of live PBMCs fold change from baseline by treatment...... 16 Table 3 Descriptive summary statistics of percent monocyte cells (CD16-) of live PBMCs fold change from baseline by treatment...... 16 Table 4 Descriptive summary statistics of percent T-cells of live PBMCs fold change from baseline by treatment...... 16 Table 5 Descriptive summary statistics of percent T-cells (CD4+) of live PBMCs fold change from baseline by treatment...... 16 Table 6 Descriptive summary statistics of percent T-cells (CD4-) of live PBMCs fold change from baseline by treatment...... 17 Table 7 Descriptive summary statistics of percent natural killer cells (CD56 bright) of live PBMCs fold change from baseline by treatment...... 17 Table 8 Descriptive summary statistics of percent natural killer cells (CD56 bright CD16+) of live PBMCs fold change from baseline by treatment...... 17 Table 9 Descriptive summary statistics of percent natural killer cells (CD56 bright CD16-) of live PBMCs fold change from baseline by treatment...... 17 Table 10 Descriptive summary statistics of percent natural killer cells (CD56 dim CD16-) of live PBMCs fold change from baseline by treatment...... 17 Table 11 Descriptive summary statistics of percent B-cells of live PBMCs fold change from baseline by treatment...... 18 Table 12 Descriptive summary statistics of percent T-cells (CD4+ CCR5 high) of live PBMCs fold change from baseline by treatment...... 18 Table 13 Descriptive summary statistics of percent T-cells (CD4- CCR5 high) of live PBMCs fold change from baseline by treatment...... 18 Table 14 Descriptive summary statistics of percent B-cells (CCR5 high) of live PBMCs fold change from baseline by treatment...... 18 Table 15 Descriptive summary statistics of percent T-cells (CD4+ CD69 high) of live PBMCs fold change from baseline by treatment...... 18 Table 16 Descriptive summary statistics of percent T-cells (CD4+-CD69 high) of live PBMCs fold change from baseline by treatment...... 19 Table 17 Descriptive summary statistics of percent natural killer cells (CD56 bright CD69 high) of live PBMCs fold change from baseline by treatment...... 19 Table 18 Descriptive summary statistics of percent natural killer cells (CD56 dim CD16- CD69 high) of live PBMCs fold change from baseline by treatment...... 19 Table 19 Descriptive summary statistics of percent B-cells (CD69 high) of live PBMCs fold change from baseline by treatment...... 19 Table 20 Descriptive summary statistics of percent T-cells (CD4+ HLA-DR+) of live PBMCs fold change from baseline by treatment...... 19

2 Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

Table 21 Descriptive summary statistics of percent T-cells (CD4- HLA-DR+) of live PBMCs fold change from baseline by treatment...... 20 Table 22 Descriptive summary statistics of monocyte cells (CD86-) mean fluorescence intensity fold change from baseline by treatment...... 20 Table 23 Descriptive summary statistics of monocyte cells (CD16+ CD86-) mean fluorescence intensity fold change from baseline by treatment...... 20 Table 24 Descriptive summary statistics of monocyte cells (CD16- CD86-) mean fluorescence intensity fold change from baseline by treatment...... 20 Table 25 Descriptive summary statistics of monocyte cells (CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 20 Table 26 Descriptive summary statistics of monocyte cells (CD16+ CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 21 Table 27 Descriptive summary statistics of monocyte cells (CD16- CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 21 Table 28 Descriptive summary statistics of T-cells (CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 21 Table 29 Descriptive summary statistics of T-cells (CD4+ CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 21 Table 30 Descriptive summary statistics of T-cells (CD4- CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 21 Table 31 Descriptive summary statistics of natural killer cells (CD56 bright CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 22 Table 32 Descriptive summary statistics of natural killer cells (CD56 bright CD16+ CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 22 Table 33 Descriptive summary statistics of natural killer cells (CD56 bright CD16- CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 22 Table 34 Descriptive summary statistics of T-cells (CD4- CD69-) mean fluorescence intensity fold change from baseline by treatment...... 22 Table 35 Descriptive summary statistics of natural killer cells (CD56 bright CD69-) mean fluorescence intensity fold change from baseline by treatment...... 22 Table 36 Descriptive summary statistics of natural killer cells (CD56 bright CD16+ CD69-) mean fluorescence intensity fold change from baseline by treatment...... 23 Table 37 Descriptive summary statistics of natural killer cells (CD56 bright CD16- CD69-) mean fluorescence intensity fold change from baseline by treatment...... 23 Table 38 Descriptive summary statistics of natural killer cells (CD56 dim CD16- CD69-) mean fluorescence intensity fold change from baseline by treatment...... 23 Table 39 Descriptive summary statistics of B-cells (CD69-) mean fluorescence intensity fold change from baseline by treatment...... 23 Table 40 Descriptive summary statistics of monocyte cells (HLA-DR) mean fluorescence intensity fold change from baseline by treatment...... 23 Table 41 Descriptive summary statistics of monocyte cells (CD16+ HLA-DR) mean fluorescence intensity fold change from baseline by treatment...... 24

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Table 42 Descriptive summary statistics of monocyte cells (CD16- HLA-DR) mean ﬂuorescence intensity fold change from baseline by treatment...... 24 Table 43 Descriptive summary statistics of Human platelet-derived growth factor concentration fold change from baseline by treatment...... 24 Table 44 Descriptive summary statistics of Human Interleukin-1 beta concentration fold change from baseline by treatment...... 24 Table 45 Descriptive summary statistics of Human Interleukin-1 receptor antagonist concentration fold change from baseline by treatment...... 24 Table 46 Descriptive summary statistics of Human Interleukin-2 concentration fold change from baseline by treatment...... 25 Table 47 Descriptive summary statistics of Human Interleukin-4 concentration fold change from baseline by treatment...... 25 Table 48 Descriptive summary statistics of Human Interleukin-5 concentration fold change from baseline by treatment...... 25 Table 49 Descriptive summary statistics of Human Interleukin-6 concentration fold change from baseline by treatment...... 25 Table 50 Descriptive summary statistics of Human Interleukin-7 concentration fold change from baseline by treatment...... 25 Table 51 Descriptive summary statistics of Human Interleukin-8 concentration fold change from baseline by treatment...... 26 Table 52 Descriptive summary statistics of Human Interleukin-9 concentration fold change from baseline by treatment...... 26 Table 53 Descriptive summary statistics of Human Interleukin-10 concentration fold change from baseline by treatment...... 26 Table 54 Descriptive summary statistics of Human Interleukin-12 (Lupus Ku autoantigen protein p70) concentration fold change from baseline by treatment...... 26 Table 55 Descriptive summary statistics of Human Interleukin-13 concentration fold change from baseline by treatment...... 26 Table 56 Descriptive summary statistics of Human Interleukin-15 concentration fold change from baseline by treatment...... 27 Table 57 Descriptive summary statistics of Human Interleukin-17 concentration fold change from baseline by treatment...... 27 Table 58 Descriptive summary statistics of Human Eotaxin concentration fold change from baseline by treatment...... 27 Table 59 Descriptive summary statistics of Human basic ﬁbroblast growth factor concentration fold change from baseline by treatment...... 27 Table 60 Descriptive summary statistics of Human granulocyte-colony stimulating factor concentration fold change from baseline by treatment...... 27 Table 61 Descriptive summary statistics of Human granulocyte macrophage-colony stimulating factor concentration fold change from baseline by treatment...... 28 Table 62 Descriptive summary statistics of Human interferon gamma concentration fold change from baseline by treatment...... 28

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Table 63 Descriptive summary statistics of Human Interferon gamma-induced protein 10 concentration fold change from baseline by treatment...... 28 Table 64 Descriptive summary statistics of Human Monocyte chemoattractant protein-1 (Monocyte Chemotactic and Activating Factor) concentration fold change from baseline by treatment. . 28 Table 65 Descriptive summary statistics of Human Macrophage Inflammatory Protein-1 alpha concentration fold change from baseline by treatment...... 28 Table 66 Descriptive summary statistics of Human Macrophage Inflammatory Protein-1 beta concentration fold change from baseline by treatment...... 29 Table 67 Descriptive summary statistics of Human RANTES concentration fold change from baseline by treatment...... 29 Table 68 Descriptive summary statistics of Human Tumor necrosis factor - alpha concentration fold change from baseline by treatment...... 29 Table 69 Descriptive summary statistics of Human Vascular endothelial growth factor concentration fold change from baseline by treatment...... 29 Table 70 Descriptive summary statistics of natural killer cells (CD56 dim CD16- CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 29 Table 71 Descriptive summary statistics of B-cells (CCR5-) mean fluorescence intensity fold change from baseline by treatment...... 30 Table 72 Descriptive summary statistics of T-cells (CD69-) mean fluorescence intensity fold change from baseline by treatment...... 30 Table 73 Descriptive summary statistics of T-cells (CD4+ CD69-) mean fluorescence intensity fold change from baseline by treatment...... 30 Table 74 Differentially expressed genes (Combined Study Groups, Day 0 vs. 1) ...... 31 Table 75 Differentially expressed genes (Combined Study Groups, Day 0 vs. 2) ...... 35 Table 76 Differentially expressed genes (Combined Study Groups, Day 0 vs. 7) ...... 42 Table 77 Differentially expressed genes (Combined Study Groups, Day 0 vs. 14) ...... 51 Table 78 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia), Day 2 vs. 0) ...... 53 Table 79 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia), Day 7 vs. 0) ...... 55 Table 80 Differentially expressed genes (vaccine study comparisons, YF-17D (Yellow Fever), Day 3 vs.0)...... 56 Table 81 Differentially expressed genes (vaccine study comparisons, YF-17D (Yellow Fever), Day 7 vs.0)...... 60 Table 82 Differentially expressed genes (vaccine study comparisons, TIV (Influenza), Day 7 vs. 0) . 62 Table 83 Differentially expressed genes (vaccine study comparisons, LAIV (Influenza), Day 3 vs. 0) . 63 Table 84 Differentially expressed genes (vaccine study comparisons, LAIV (Influenza), Day 7 vs. 0) . 65 Table 85 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia) Day 2 vs. YF-17D (Yellow Fever) Day 3) ...... 65 Table 86 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia) Day 7 vs. YF-17D (Yellow Fever) Day 7) ...... 69

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Table 87 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia) Day 2 vs. TIV (Influenza) Day 3) ...... 69 Table 88 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia) Day 7 vs. TIV (Influenza) Day 7) ...... 70 Table 89 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia) Day 2 vs. LAIV (Influenza) Day 3) ...... 71 Table 90 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tu- laremia) Day 7 vs. LAIV (Influenza) Day 7) ...... 72 Table 91 Combination of genes differentiating between responders and non-responders (Microag- glutination titer, Day 2) ...... 74 Table 92 Combination of genes differentiating between responders and non-responders (Microag- glutination titer, Day 7) ...... 76 Table 93 Canonical correlation analysis summary statistics ...... 76

Conﬁdential/Proprietary Information -6- List of Figures

Figure 1 Scatter plot of log2 fold changes of signiﬁcant genes (DVC-LVS vs. USAMRIID-LVS, Day 7, 14)...... 77 Figure 2 Gene cluster dendrogram with bootstrap probabilities (Combined Study Groups, Day 1-14) 78

Figure 3 Gene cluster time trends of baseline log2 fold change by study group (Combined Study Groups, Day 1-14) ...... 79

Figure 4 Gene cluster time trends of baseline log2 fold change by study group (Combined Study Groups, Day 1-14) ...... 80

Figure 5 Gene cluster time trends of baseline log2 fold change by study group (Combined Study Groups, Day 1-14) ...... 81

Figure 6 Time trends of mean log2 fold change and associated 95% bootstrap conﬁdence intervals for gene clusters identiﬁed in subject-level heatmaps...... 82 Figure 7 Number of subjects that pass a certain immune response cut off by assay...... 83 Figure 8 Canonical correlation scree plots...... 84

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1 Introduction

This appendix provides supporting information for the manuscript entitled "‘Systems vaccinology for a live attenuated tularemia vaccine reveals unique transcriptional signatures that predict humoral and cellular immune responses"’.

2 Supplemental methods

2.1 Study Design

This laboratory substudy was a systems biology study of the human response to two lots of tularemia vaccines assessed in a phase 2 clinical trial [1]. Tularemia is caused by Franciscella tularensis, a gram- negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Processes. To assess this, a phase 2 randomized clinical trial was conducted comparing the new lot (DVC-LVS) produced by DynPort Vaccine Company to the existing vaccine that has been in use by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID-LVS) for decades. The vaccines were delivered by scariﬁcation to 228 participants in the main study, which evaluated vaccine safety, reactogenicity, take and Tularemia-speciﬁc microagglutination titer on Days 0 (baseline), 8, 14, 28, 56, and 180. For this substudy, blood samples were obtained for 42 healthy male and female subjects aged 18 to 45 years old, enrolled in [1]. Laboratory assessments on Days 0, 1, 2, 7, and 14 included gene expression based on PBMC RNA using microarrays, serum cytokine/chemokine concentration measurements, and immune cell phenotyping (DC/monocyte/lymphocyte cells). T-cell activation was evaluated on Days 0, 14, 28, 56, and 180. Day 180 also included an assessment of T-cell proliferation.

2.2 Microarray experiment

Affymetrix High-throughput (HT) Perfect Match (PM) Array GeneChips were run in a 96 array plate con- ﬁguration (96 samples per HT array). Each individual array contained 54,715 probe sets and 536,460 perfect match (PM) probes (on average 9.8 probes per probe set). HT PM Array Plates only contain PM probes. Mismatch probes (MM) are not included. Three 96 HT array plates were run producing data for 205 samples (the last 96 HT array contained data for 13 samples). Plates were run on three different days (10/11/2011, 11/8/2011, and 11/15/2011). For ﬁve samples array data was not produced: subject T02HC051 was missing Day 1; T02HC115 was missing Days 2, 7, and 14; T02HC118 was missing Day 0. All of the other 39 subjects had array data for all 5 time points (Day 0, 1, 2, 7, 14).

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2.3 Cell mediated immunity experiments

Phenotyping of immune cell subpopulations This assay included 3 panels. It was performed pre- vaccination (Day 0), and at Days 1, 2, 7 and 14 post-vaccination. Results were measured in percent live PBMCs as well as mean ﬂuorescence intensity.

For the dendritic cell panel, samples were ﬁrst gated to exclude dead cells, debris, and doublets. Total Dendritic cells (DCs) were then deﬁned as linage negative (CD3-CD14-CD16-CD19-CD20-CD56-) and HLADR+. DCs were then divided into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) subset based on CD11c and CD123 expression, respectively. mDCs were then further subdivided based on BDCA1 expression. All populations were then analyzed for CCR7, CD86, CD11b, and HLADR expression.

For the monocyte panel, samples were ﬁrst gated to exclude dead cells, debris, and doublets and then B-cells and T-cells were excluded by CD19 and CD3 expression. HLADR+ cells were then deﬁned as monocytes. Monocytes were then subdivided into CD14+ CD16- classical monocytes, CD14+ CD16+ intermediate monocytes, and CD14 dim CD16+ non-classical monocytes. All populations were then analyzed for CD86, CCR5, and HLADR expression.

For the lymphocyte panel, samples were first gated to exclude dead cells, debris, and doublets. CD14+ cells are excluded and CD14- cells were divided into CD3+ (T cells), CD19+ (B cells), and CD3- CD19- subsets. CD3+ cells were then divided into CD4+ and CD4- subsets and further analyzed for HLADR expression. The CD3-CD19- population was divided into CD56 bright (CD56 high CD16-) and CD56 dim (CD56 mid CD16+) natural killer (NK) cell subsets. All populations were then analyzed for CCR5 and CD69 expression. Expression of CCR7, CD86, CD11b, HLADR, CCR5 and CD69 was reported as mean fluorescence intensity (MFI). Background fluorescence was subtracted using isotype controls for all antibodies but anti HLADR.

T-Cell activation by phenotyping Phenotyping of T-cell activation was performed with whole blood samples at Day 0 (baseline), and Days 1, 2, 7, 14, 28 and 56 post-vaccination. Lymphocytes were identified based on forward scatter (FSC) and side scatter (SSC) properties. CD3+CD4+CD8- cells and CD3+CD4-CD8+ cells were defined as CD4 and CD8 T-cells. Activated T-cells were defined by co-expression of CD38 and HLA-DR (surface staining) or co-expression of Ki67 and Bcl-2 (intracellular staining) separately. Results were measured in percent live PBMCs.

T-cell proliferation assay The CFSE proliferation assay was performed using PBMCs from participants at Day 180 post-vaccination. Cells were labeled with CFSE and stimulated for 6 days with formalin-inactivated Tularemia Type B strain LVS or Type A strain SCHU S4 and then analyzed by

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FACS. Lymphocytes, CD4 and CD8 T-cells were gated as described above. T-cell proliferation potential was determined as percent of CFSE low cells on CD4 and CD8 T cells separately and was normalized by subtracting percent of CFSE low cells obtained for negative (unstimulated) controls.

Serum cytokines/chemokines Human plasma cytokines were analyzed for Days 0, 1, 2, 7 and 14 using the Bio-Plex Pro Human Cytokine 27-plex Assay (Bio-Rad) according to manufacturer’s instruc- tion and are represented as pg/ml.

2.4 Microarray data preprocessing

Probe set annotations for HT HG-U133 Plus PM GeneChips were downloaded from the Affymetrix website (Release 34, 10/23/13). Due to missing MM probes, MAS 5.0-based average background and scale factors could not be calculated as outlined in the SAP. Instead, a median scaling factor for each sample was calculated by first calculating a scaling factor for each probe on the log2 scale (median across all samples divided by probe intensity) followed by calculating the median of all probe scaling factors per sample. High values indicate that a library had typically lower probe values and vice versa. RNA quality and transcript truncation was evaluated by using β-actin and GAPDH housekeeping control probe sets that target different regions of the same gene (30 end of transcript, middle (M) portion of the transcript, and 50 end of transcript). 30/50 ratios and M/50 ratios were calculated for each individual array. Hybridization and overall signal quality for each array was evaluated using 4 Affymetrix spike-in probe sets (BioB, BioC, BioD, CreX) that are added to the experiment with increasing RNA concentrations (as listed from low to high). Median intensity was used to summarize intensities per probe set and log2 value of the ratio was reported. The slope (proxy for hybridization strength) was estimated for each sample by fitting a linear regression model. RNA-degradation was inspected by plotting average probe intensities in the 5’ to 3’ direction (the first 8 probes were included per probe set). The RNA degradation slope was estimated for each sample by fitting a linear regression model. The Robust Multichip Average (RMA) algorithm (Irizarry et al., 2003) was used to obtain background-corrected and quantile-normalized probe-level intensities. Probe and probe-level log2 intensity distributions were investigated using boxplots, probability density function (PDF) plots, and log expression (RLE) boxplots (Brettschneider et al., 2008). The ComBat algorithm [2] using the parametric empirical Bayes option was applied to adjust the probe-level data for batch effects. Extreme outliers were removed from the probe level data and background correction, quantile normalization, and batch correction was rerun in ˆ S the specified order. Next, probe sets with a sample coefficient of variation (CV = xˆ ) in the lower 25% quantile were filtered out.

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2.5 Differential gene analysis

A two-sided paired t-test was applied to identify significantly up/down-regulated genes from baseline (Day 0 versus Day 1, 2, 7, 14). The paired test was carried out separately for each study group as well as for combined study groups. In addition, log2 fold changes per study visit were compared between study groups using a two-sided Welch’s t-test. To compensate for multiple testing, the false discovery rate (FDR) which controls the false positive rate among significantly differentially expressed genes was calculated using the qvalue R package. Genes with a q-value ≤ 0.05 and a fold change of ≥ 1.5-fold (up or down regulation) were deemed to be significantly differentially expressed.

2.6 Determination of robust gene clusters log2 fold changes of genes that were differentially expressed for a certain study group at any post baseline day were used as input for gene clustering. Uncentered Pearson correlation distance was used as distance measure. Pairwise distances between log2 changes were calculated separately for each vaccine group and post baseline day (Day 1, 2, 7, 14) as well as for all study days (Day 1- 14). Clusters were obtained using the hierarchical complete linkage clustering algorithm. To evaluate robustness of gene clusters, multiscale bootstrapping (Suzuki and Shimodaira, 2006) was carried out using varying dataset sizes (0.4*N, 0.5*N, 0.6*N, 0.7*N, 0.8*N, 0.9*N, 1*N, 1.1*N, 1.2*N, 1.3*N; where N stands for the respective dataset size). For each dataset size bin, 1,000 bootstrap samples were obtained, and bootstrap probabilities and p-values were calculated. The unbiased bootstrap probability cut-off was set to 0.05 and the maximum distance to form a signiﬁcant cluster was set to 0.5 (equivalent to minimum uncentered Pearson correlation of 0.5). Clusters that were formed at larger distances were excluded.

2.7 Gene set enrichment analysis

Gene set enrichment analysis was performed using the Java implementation (Version 2.1.0, downloaded 01/23/2015 from http://www.broadinstitute.org/gsea) of the GSEA algorithm (GSEAPreranked method) to detect enriched gene sets [3]. Ensemble genes were grouped and analyzed based on 8,101 known gene sets obtained from the KEGG database (Version 70.0 (06/09/2014), [4]) and MSigDB (Ver- sion 4.0 (05/31/2013), [5]). The MSigDB gene set collection was comprised of GO Biological Processes, GO Cellular Components, GO Molecular Functions, Reactome Pathway, BioCarta Pathway, Chemical/- Genetic Perturbations, and Immunologic Signature gene sets. GSEA analysis was carried out separately for each post-vaccination day, comparison group (post-vaccination vs. baseline for DVC-LVS, post-vaccination vs. baseline for USAMRIID-LVS, and post-vaccination vs. baseline for the combined groups, as well as DVC-LVS vs. USAMRIID-LVS for each post-vaccination day). Probe set IDs were converted to Ensembl gene IDs based on Affymetrix HG U133 release 34 probe set annotations. To increase annotation coverage, for genes that did not have Affymetrix Ensembl gene IDs assignments,

Confidential/Proprietary Information -11- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. if available, common name to gene ID mappings were obtained from the HUGO Gene Nomenclature Committee (www.genenames.org, downloaded 05/12/2015). Ranked lists of Ensembl gene IDs based on decreasing t-statistic were used as input for Chemical/Genetic Perturbations, and Immunologic Sig- nature gene. For all other gene set collections, the absolute t-statistic was used. In either case, before generating the lists, the largest absolute t-statistic was used for Ensembl gene IDs that mapped to multiple probe sets. Except for Chemical/Genetic Perturbations, and Immunologic Signature gene sets which contain directional information, the absolute t-statistic was used. Program specifications were as follows: random seed was specified as 149, collapse was set to false, the minimum and maximum gene set size was not restricted (set to 1 and 10000, respectively), and the number of permutations was set to 10,000. To adjust for testing multiple gene sets per category type, the Benjamini-Hochberg procedure was applied to each list. For Chemical/Genetic Perturbation and Immunologic Signature collections, with many more gene sets compared to the other gene set collections, a FDR < 0.01 was applied to determine significant enrichment. For all other collections, a cut off of FDR < 0.1 was used. Enrich- ment trends across post-vaccination days and comparison groups were visualized using heatmaps and binary Jaccard-distance based complete-linkage hierarchical clustering.

2.8 Regularized logistic regression analysis

As there is no a priori knowledge about the correlates of protection for these vaccines, responders, non-responders, and subjects with high baseline were arbitrarily defined. The positive cut off for immune response thresholds for responders based on the percentage of activated CD4+, CD8+ T-cells and microagglutination titer was defined as three standard deviations (SD) above the mean of all baseline samples. Concurrently, a minimum sample size of 10 subjects in either response group (responders and non-responders) was required. The minimum subject criterion was met for responders and non-responders when combining vaccine study arms based on CD8+ T-cell activation and microagglutination titer but not for percent activated CD4+ T-cells. As the SAP allowed for flexibility in the choice of the cut off, the numbers of responders and non-responders in the combined data set were plotted for different SD cut offs to see if an alternative cut off can be identified that meets the minimum subject requirement. Based on the CD4+ plot, a cut off of 2 SD was chosen to define a positive CD4+ response. The classification for subjects with persistent T-cell responses (3 SD above the baseline mean at Day 7, 14, and 28) versus transient T-cell responses (3 SD above the baseline mean at Day 7 and 14 but below this cut off at Day 28) did not meet the minimum number of required subjects for CD4+ and CD8+ for any SD cut off. Thus, the comparison of transient versus persistent subjects was not carried out. The following criteria were used to define assay-specific responders and non-responders:

1. classiﬁcation based on Tularemia-speciﬁc microagglutination titer

(a) responder: a subject in which tularemia vaccine induces an increase in Tularemia-speciﬁc log-transformed microagglutination titer that is 3 SD above the mean of all log-transformed baseline values, at any of the following time points: Days 14 or 28.

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(b) non-responder: a subject in which tularemia vaccine does not induce an increase in tularemia speciﬁc log-transformed microagglutination titer that is 3 SD above the mean of all log-transformed baseline values, at any of the following time points: Days 14 or 28. (c) subject with high baseline: a subject with a log-transformed baseline value that is 3 SD above the mean of all log-transformed baseline values.

For each post-vaccination Day (1, 2, 7, 14) and assay-specific classification, a regularized logistic regression model was fit to identify gene responses that distinguish between responders and non responders using the glmnet R package (Version 2.0-2). Before fitting the models, the predictor variable set (probe sets) was processed as follows:

1. probe sets corresponding to the same gene (same gene name) were collapsed by retaining the probe set per gene that had the highest absolute mean fold change from baseline at the respective post vaccination- day.

2. collapsed probe sets with an absolute fold change ≥ 1.5 were retained and used as predictors for the respective model.

To avoid overfitting (n << p and collinearity among gene responses) and facilitate variable selection, an elastic net regularization step (combination of L1 Lasso and L2 ridge penalization, α = 0.5) was included as part of the fitting procedure. Five-fold cross validation was used to determine the optimum regularization parameter λ based on the minimum average model deviance across folds. In addition, the mean misclassification error across folds was determined for the optimal λ and provided as additional cross-validation statistic. The five random folds were stratified by positive and negative responders, i.e. the overall proportion of positive/negative responders was maintained for each random fold. The seed was set to 20151121.

2.9 Regularized canonical correlation analysis

To identify patterns that explain associations between changes in gene expression and peak changes in immunogenicity outcomes (IMO), multivariate regularized Canonical Correlation Analysis (CCA) was carried out separately for Days 1, 2, 7, and 14. CCA identiﬁes linear combinations of the original variables (referred to as canonical variates) that maximize the inter-set correlation (here gene and immunogenicity variable sets). Planned immunogenicity variables included peak baseline fold change in %T-cell activation (CD8+ and CD4+ cells), T-cell proliferation at Day 180 (CD8+ and CD4+ cells), and peak baseline fold change in microagglutination titer. T-cell proliferation data was not included as part of the models as proliferation data for 11 subjects was missing (the data had not been collected). Before ﬁtting the CCA models, the gene expression variable set was processed as follows:

1. probe sets corresponding to the same gene (same gene name) were collapsed by retaining the probe set per gene that had the highest absolute mean fold change from baseline for the respective post vaccination- day.

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2. collapsed probe sets with an absolute fold change ≥ 1.5 were retained and used as gene variable set for the correlation analysis.

The 5 IMO variables were encoded as follows:

– CD4H: subject-speciﬁc peak fold change in %CD3+ CD4+ CD38+ HLA-DR+ T-cells (Days 14, 28, 56, 180).

– CD4B: subject-speciﬁc peak fold change in %CD3+ CD4+ BCL2+ KI67+ T-cells (Days 14, 28, 56, 180).

– CD8H: subject-speciﬁc peak fold change in %CD3+ CD8+ CD38+ HLA-DR+ T-cells (Days 14, 28, 56, 180).

– CD8B: subject-speciﬁc peak fold change in %CD3+ CD8+ BCL2+ KI67+ T-cells (Days 14, 28, 56, 180).

– MAGL: subject-speciﬁc peak fold change in Tularemia-speciﬁc microagglutination titer (Days 14, 28, 56, 180).

Prior to CCA, immunogenicity variables were transformed using the Box-Cox transformation to make their distributions more symmetric and unimodal (while normality is not required, it optimizes the distri- butional information used as part of the modeling process). To avoid over fitting (n« g and collinearity among genes) a regularization step was applied. Optimal regularization parameters were estimated using leave-one-out cross validation. Significant canonical variate pairs were identified by manually in- specting scree plots. Individual variables were correlated against their significant canonical variates to obtain canonical loadings. Canonical loadings were squared to obtain the proportion of explained variance. Canonical loadings for each variable set were plotted and variables with low explained variance were filtered out (correlation < 0.5 or explained variance < 25%).

2.10 Comparisons with viral vaccine microarray studies

RMA-normalized expression data obtained from yellow fever (YF-17D) vaccinees (Day 0, 3, 7) as well as trivalent influenza vaccine (TIV) (Day 0, 3, 7), and live attenuated influenza vaccine (LAIV) (Day 0, 3, 7) vaccinees were provided by Emory University. For each vaccine study, probe sets with a coefficient of variation (CV) higher than the lower quartile of all CVs were retained. Due to different Affymetrix array types and non-matching probe information (HG-U133 PM for 10-0019 Tularemia vaccine data and HG133 Plus 2 for YF-17D, TIV, and LAIV microarray data), the mean log2 fold change across gene sets with the same gene symbol (based on Affymetrix release 34 probe set annotations) was used for the comparative analysis. For each vaccine study and post-vaccination day, a paired-t test was applied to identify genes that were differential expressed from baseline. A Welch t-test was used to identify differential fold changes between vaccine studies (Day 2 responses following DVC-LVS/USAMRIID-LVS vaccination were compared to Day 3 responses following YF-17D, TIV, or LAIV vaccination). The same fold change and FDR cut offs as described in Section 2.5 were used. For gene set enrichment analysis, gene symbols were mapped to Ensembl gene IDs using Affymetrix HG-U133 PM and Hugo (accessed 05/12/2015) mappings. Only gene symbols represented in the 10-0019 Tularemia expression data set were analyzed using GSEA. For Ensembl gene IDs that mapped to multiple gene symbols, the

Conﬁdential/Proprietary Information -14- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. largest absolute t statistic was used. Genes were then ranked based on absolute t statistic and GSEA analysis was carried out as described in Section 2.7. The DVC/USAMRIID-LVS data was pooled when identifying enriched gene sets as well as DE genes. Tularemia vaccine group membership was retained and displayed in subject-level heatmaps when comparing differential gene lists.

2.11 Cell mediated immunity analysis

MFI values less than 0 after normalization of background ﬂuorescence were set to 0. MFI values of 0 were imputed to 1 for fold calculations only. Similarly, percent cell activation values of 0 were imputed to 0.01 for fold change calculations only. Cytokines with concentrations less than the experimental lower limit of quantiﬁcation (LLOQ) were imputed to 1/2 LLOQ. A 95% CI for the median measurement as well as median fold change from baseline for each time point and treatment group was obtained for each assay and marker combination using the bootstrap method with 1,000 bootstrap replicates each.

3 Supplemental results

Tables

Conﬁdential/Proprietary Information -15- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n34 Min35 0.6535 0.53 Q135 0.88 0.33 0.91 0.34 Median 0.98 0.62 (95% (0.90,1.14) CI) 1.09 0.66 (0.95,1.24) 0.79 (0.76,0.92) 0.78 (0.68,0.94) Q3 1.24n 1.3234 1.57 1.11 Min Max 35 0.85 1.73 1.0235 0.84 2.07 Q135 0.99 0.52 1.92 0.99 0.35 Median 1.23 0.93 (95% (1.05,1.32) CI) 1.41 0.71 (1.16,1.76) 1.13 (0.98,1.26) 0.91 (0.82,1.12) Q3 1.43n 1.8134 2.38 1.32 Min Max 35 0.59 3.16 1.2735 0.51 3.93 Q135 0.83 0.31 2.68 0.87 0.28 Median 0.96 0.59 (95% (0.88,1.12) CI) 1.03 0.63 (0.92,1.21) 0.76 (0.65,0.90) 0.73 (0.68,0.93) Q3 1.23n 1.3134 1.63 1.08 Min Max 35 0.87 1.75 1.0435 0.73 2.04 Q135 0.97 0.83 1.92 0.95 0.78 Median 1.01 0.96 (95% (0.97,1.04) CI) 0.99 1.03 (0.97,1.00) 1.05 (1.01,1.09) 1.09 (1.04,1.10) Q3 1.10n 1.0234 1.27 1.14 Min Max 35 0.73 1.29 1.1335 0.79 1.42 Q135 0.98 0.75 1.44 0.97 0.71 Median 1.04 0.95 (95% (1.02,1.09) CI) 1.00 1.02 (0.98,1.04) 1.08 (1.00,1.14) 1.08 (1.04,1.20) Q3 1.12n 1.0634 1.44 1.25 Min Max 0.56 1.43 1.22 1.57 Q1 0.96 1.53 Median 1.02 (95% (0.97,1.06) CI) Q3 1.09 1.34 Max USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n15 Min16 0.7416 0.53 Q116 0.92 0.33 0.84 0.34 Median 1.11 0.61 (95% (0.93,1.35) CI) 1.03 0.64 (0.84,1.24) 0.78 (0.62,1.15) 0.77 (0.63,1.05) Q3 1.39n 1.2515 1.57 1.18 Min Max 16 0.87 1.45 1.0816 0.84 2.06 Q116 1.24 0.83 1.92 0.99 0.61 Median 1.32 1.09 (95% (1.22,2.05) CI) 1.68 0.83 (0.99,1.99) 1.22 (1.10,1.33) 0.99 (0.79,1.47) Q3 2.06n 2.0115 2.38 1.37 Min Max 16 0.72 2.54 1.5716 0.51 3.93 Q116 0.89 0.31 2.68 0.77 0.28 Median 1.06 0.55 (95% (0.91,1.27) CI) 1.00 0.54 (0.78,1.21) 0.71 (0.56,1.12) 0.69 (0.55,1.05) Q3 1.33n 1.2315 1.63 1.10 Min Max 16 0.87 1.37 1.0816 0.82 2.03 Q116 0.96 0.83 1.92 0.98 0.87 Median 1.00 0.94 (95% (0.97,1.07) CI) 1.00 1.03 (0.98,1.04) 1.04 (0.95,1.14) 1.09 (1.02,1.15) Q3 1.06n 1.0315 1.14 1.14 Min Max 16 0.73 1.29 1.1516 0.79 1.42 Q116 0.94 0.75 1.44 0.99 0.83 Median 1.02 0.94 (95% (0.98,1.11) CI) 1.01 1.00 (0.99,1.09) 1.04 (0.94,1.18) 1.08 (1.00,1.22) Q3 1.10n 1.0915 1.23 1.19 Min Max 0.88 1.39 1.22 1.57 Q1 0.96 1.45 Median 1.00 (95% (0.96,1.06) CI) Q3 1.06 1.34 Max DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of percent T-cells of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent T-cells (CD4+) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent monocyte cells of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent monocyte cells (CD16-) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent monocyte cells (CD16+) of live PBMCs fold change from baseline by treatment. Table 4: Table 5: Table 1: n19 Min19 0.6519 0.60 Q119 0.85 0.53 0.98 0.54 Median 0.94 0.67 (95% (0.86,1.14) CI) 1.16 0.69 (1.02,1.34) 0.80 (0.72,0.92) 0.78 (0.70,0.94) Q3 1.14n 1.3619 1.46 0.98 Min Max 19 0.85 1.73 0.9519 0.85 2.07 Q119 0.94 0.52 1.57 1.04 0.35 Median 1.05 0.77 (95% (0.96,1.23) CI) 1.28 0.63 (1.08,1.72) 0.95 (0.81,1.13) 0.88 (0.66,1.17) Q3 1.26n 1.7419 1.56 1.22 Min Max 19 0.59 3.16 1.1719 0.53 2.40 Q119 0.81 0.48 2.57 0.94 0.54 Median 0.95 0.63 (95% (0.82,1.12) CI) 1.13 0.70 (0.96,1.32) 0.77 (0.67,0.90) 0.73 (0.70,0.92) Q3 1.12n 1.3319 1.47 0.98 Min Max 19 0.88 1.75 0.9519 0.73 2.04 Q119 0.97 0.90 1.57 0.92 0.78 Median 1.02 1.00 (95% (0.98,1.11) CI) 0.97 1.03 (0.93,1.00) 1.05 (1.00,1.12) 1.08 (1.04,1.12) Q3 1.12n 1.0019 1.27 1.12 Min Max 19 0.93 1.19 1.1219 0.83 1.39 Q119 1.03 0.88 1.43 0.94 0.71 Median 1.05 1.02 (95% (1.03,1.13) CI) 0.99 1.03 (0.94,1.03) 1.11 (1.03,1.26) 1.08 (1.03,1.20) Q3 1.15n 1.0419 1.44 1.29 Min Max 0.56 1.43 1.21 1.48 Q1 0.98 1.53 Median 1.02 (95% (0.99,1.09) CI) Q3 1.11 1.16 Max Table 3: Table 2: Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1

Conﬁdential/Proprietary Information -16- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n35 Min35 0.6235 0.54 Q1 0.88 0.85 0.90 Median 0.94 0.97 (95% (0.91,1.00) CI) 1.00 (0.94,1.06) 1.06 (1.02,1.11)n Q3 1.0134 1.13 Min35 0.46 1.16 1.13 Max 35 0.55 1.89 Q135 0.73 0.56 1.45 0.79 0.39 Median 0.87 0.80 (95% (0.77,0.97) CI) 0.89 0.77 (0.84,1.02) 0.91 (0.82,1.06) 0.93 (0.86,1.09) Q3 1.01n 1.0734 1.58 1.07 Min Max 35 0.50 1.42 1.1935 0.44 1.51 Q135 0.74 0.57 1.88 0.76 0.22 Median 0.90 0.83 (95% (0.83,1.00) CI) 0.95 0.75 (0.81,1.08) 0.92 (0.89,1.11) 1.04 (0.85,1.21) Q3 1.08n 1.1634 1.62 1.22 Min Max 35 0.43 1.92 1.3235 0.58 2.24 Q135 0.73 0.53 2.53 0.77 0.41 Median 0.87 0.81 (95% (0.77,0.96) CI) 0.92 0.80 (0.83,0.99) 0.92 (0.83,1.03) 0.92 (0.85,1.06) Q3 1.01n 1.0634 1.64 1.10 Min Max 35 0.45 1.41 1.1835 0.44 1.52 Q135 0.65 0.56 1.66 0.71 0.38 Median 0.80 0.72 (95% (0.72,1.04) CI) 0.87 0.75 (0.73,0.99) 0.87 (0.78,1.01) 0.90 (0.82,1.00) Q3 1.10n 1.0734 2.04 1.08 Min Max 0.35 2.17 1.05 1.78 Q1 0.89 2.40 Median 1.09 (95% (0.97,1.16) CI) Q3 1.27 3.27 Max USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n16 Min16 0.8216 0.54 Q1 0.92 0.94 0.88 Median 0.96 1.00 (95% (0.91,1.01) CI) 0.99 (0.88,1.15) 1.06 (0.99,1.11)n Q3 1.0115 1.16 Min16 0.55 1.15 1.12 Max 16 0.57 1.89 Q116 0.73 0.71 1.45 0.85 0.49 Median 0.86 0.80 (95% (0.74,0.96) CI) 0.96 0.75 (0.85,1.06) 0.90 (0.79,1.02) 0.94 (0.75,1.09) Q3 0.96n 1.0615 1.34 1.02 Min Max 16 0.51 1.42 1.1216 0.44 1.14 Q116 0.71 0.57 1.61 0.90 0.41 Median 0.90 0.79 (95% (0.73,1.08) CI) 1.05 0.78 (0.86,1.15) 0.91 (0.81,1.15) 1.10 (0.78,1.31) Q3 1.04n 1.1615 1.50 1.16 Min Max 16 0.51 1.57 1.3416 0.58 2.24 Q116 0.74 0.59 1.88 0.86 0.52 Median 0.86 0.83 (95% (0.75,0.93) CI) 0.97 0.78 (0.86,1.05) 0.90 (0.83,1.00) 0.94 (0.76,1.06) Q3 0.93n 1.0515 1.32 1.01 Min Max 16 0.61 1.41 1.0916 0.57 1.15 Q116 0.67 0.59 1.65 0.71 0.41 Median 0.81 0.74 (95% (0.63,1.11) CI) 0.91 0.70 (0.70,1.06) 0.90 (0.77,1.13) 0.90 (0.72,1.01) Q3 1.18n 1.0715 2.04 1.14 Min Max 0.35 2.17 1.05 1.78 Q1 0.92 2.40 Median 1.09 (95% (0.97,1.21) CI) Q3 1.25 3.27 Max DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of percent T-cells (CD4-) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent natural killer cells (CD56 bright) of live PBMCs fold change from baseline by treatment. Table 6: Descriptive summary statistics of percent natural killer cells (CD56 dim CD16-) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent natural killer cells (CD56 bright CD16-) of live PBMCs fold change from baseline by treatment. n19 Min19 0.6219 0.78 Q1 0.87 0.85 0.94 Median 0.93 0.96 (95% (0.88,1.01) CI) 1.03 (0.94,1.12) 1.07 (0.97,1.13)n Q3 1.0119 1.12 Min19 0.46 1.16 1.13 Max 19 0.55 1.30 Q119 0.75 0.56 1.36 0.75 0.39 Median 0.92 0.80 (95% (0.77,1.02) CI) 0.86 0.79 (0.75,1.01) 1.02 (0.81,1.30) 0.92 (0.79,1.19) Q3 1.04n 1.0919 1.58 1.31 Min Max 19 0.50 1.42 1.2319 0.44 1.51 Q119 0.79 0.59 1.88 0.76 0.22 Median 0.90 0.90 (95% (0.83,1.08) CI) 0.83 0.74 (0.76,1.08) 1.04 (0.91,1.27) 1.00 (0.74,1.18) Q3 1.13n 1.1319 1.62 1.28 Min Max 19 0.43 1.92 1.2519 0.58 1.91 Q119 0.73 0.53 2.53 0.76 0.41 Median 0.93 0.80 (95% (0.75,1.02) CI) 0.83 0.81 (0.77,0.98) 1.00 (0.80,1.25) 0.92 (0.81,1.19) Q3 1.03n 1.0319 1.64 1.27 Min Max 19 0.45 1.39 1.2319 0.44 1.52 Q119 0.66 0.56 1.66 0.73 0.38 Median 0.80 0.72 (95% (0.67,1.05) CI) 0.87 0.78 (0.74,1.01) 0.82 (0.76,1.05) 0.90 (0.78,1.05) Q3 1.06n 1.0719 1.55 1.05 Min Max 0.42 1.50 1.05 1.70 Q1 0.86 2.32 Median 1.10 (95% (0.92,1.20) CI) Q3 1.30 1.83 Max Descriptive summary statistics of percent natural killer cells (CD56 bright CD16+) of live PBMCs fold change from baseline by treatment. Table 7: Table 10: Table 9: Table 8: Study Visit Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1

Conﬁdential/Proprietary Information -17- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n35 Min35 0.3135 0.47 Q1 0.82 0.29 0.85 Median 1.05 0.74 (95% (0.83,1.15) CI) 1.15 (0.95,1.29) 0.93 (0.79,1.05)n Q3 1.4334 1.38 Min35 0.06 2.61 1.19 Max 35 0.45 2.19 Q135 0.85 0.17 2.46 0.73 0.55 Median 0.99 0.68 (95% (0.89,1.28) CI) 0.94 0.83 (0.80,1.22) 0.88 (0.78,1.18) 1.00 (0.85,1.19) Q3 1.46n 1.3634 14.27 1.31 Min Max 35 0.09 2.63 1.3235 0.26 5.83 Q135 0.78 0.31 2.80 0.65 0.50 Median 1.00 0.62 (95% (0.88,1.21) CI) 0.87 0.85 (0.79,1.03) 0.89 (0.68,1.07) 1.07 (0.88,1.09) Q3 1.45n 1.2334 5.97 1.34 Min Max 35 0.14 2.51 1.2335 0.27 3.25 Q135 0.65 0.21 4.28 0.65 0.37 Median 1.00 0.63 (95% (0.70,1.17) CI) 0.81 0.73 (0.75,0.97) 0.83 (0.65,1.04) 0.88 (0.77,1.24) Q3 1.25n 1.1334 1.94 1.19 Min Max 35 0.11 1.70 1.3735 0.56 2.65 Q135 0.85 0.50 2.16 0.92 0.48 Median 1.05 0.77 (95% (0.94,1.25) CI) 1.06 0.78 (0.95,1.21) 0.94 (0.85,1.12) 0.93 (0.81,1.03) Q3 1.39n 1.3534 4.85 1.23 Min Max 0.26 2.86 1.24 2.90 Q1 0.83 2.81 Median 1.00 (95% (0.89,1.13) CI) Q3 1.17 2.63 Max USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n16 Min16 0.3116 0.47 Q1 0.80 0.40 0.96 Median 1.10 0.73 (95% (0.82,1.56) CI) 1.21 (1.00,1.41) 1.01 (0.68,1.15)n Q3 1.5615 1.42 Min16 0.64 2.61 1.17 Max 16 0.62 2.19 Q116 0.97 0.48 1.68 0.73 0.61 Median 1.29 0.65 (95% (1.05,1.62) CI) 1.12 0.93 (0.73,1.27) 0.99 (0.67,1.27) 1.02 (0.95,1.28) Q3 1.76n 1.3015 14.27 1.31 Min Max 16 0.61 2.00 1.2816 0.26 5.83 Q116 0.91 0.31 2.26 0.72 0.51 Median 1.27 0.63 (95% (0.93,1.70) CI) 0.89 0.89 (0.67,1.26) 0.88 (0.63,1.07) 1.00 (0.90,1.12) Q3 1.62n 1.2915 5.97 1.10 Min Max 16 0.39 1.96 1.1216 0.27 1.96 Q116 0.56 0.21 2.55 0.55 0.37 Median 1.08 0.51 (95% (0.59,1.50) CI) 0.80 0.62 (0.55,1.14) 0.88 (0.51,1.21) 0.77 (0.62,1.11) Q3 1.47n 1.1615 1.79 1.19 Min Max 16 0.70 1.70 1.1416 0.58 2.65 Q116 0.97 0.50 2.16 0.92 0.48 Median 1.19 0.75 (95% (0.95,1.36) CI) 1.06 0.80 (0.93,1.27) 0.89 (0.76,0.96) 0.96 (0.81,1.06) Q3 1.38n 1.2615 4.85 0.97 Min Max 0.72 1.78 1.07 1.26 Q1 0.90 2.26 Median 1.00 (95% (0.88,1.17) CI) Q3 1.18 2.63 Max DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of percent B-cells of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent B-cells (CCR5 high) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent T-cells (CD4- CCR5 high) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent T-cells (CD4+ CD69 high) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent T-cells (CD4+ CCR5 high) of live PBMCs fold change from baseline by treatment. Table 11: n19 Min19 0.6119 0.47 Q1 0.82 0.29 0.84 Median 1.02 0.74 (95% (0.82,1.13) CI) 1.02 (0.84,1.29) 0.86 (0.75,1.02)n Q3 1.1419 1.30 Min19 0.06 2.55 1.15 Max 19 0.45 1.96 Q119 0.76 0.17 2.46 0.75 0.55 Median 0.94 0.72 (95% (0.79,1.01) CI) 0.83 0.81 (0.77,1.34) 0.87 (0.75,1.24) 0.88 (0.82,1.39) Q3 1.10n 1.3619 1.93 1.29 Min Max 19 0.09 2.63 1.4619 0.33 2.57 Q119 0.78 0.43 2.80 0.65 0.50 Median 0.91 0.62 (95% (0.78,1.13) CI) 0.84 0.84 (0.68,1.15) 0.89 (0.63,1.36) 1.08 (0.85,1.24) Q3 1.13n 1.1719 1.93 1.41 Min Max 19 0.14 2.51 1.3019 0.37 3.25 Q119 0.68 0.22 4.28 0.73 0.37 Median 0.93 0.66 (95% (0.70,1.19) CI) 0.82 0.81 (0.75,0.97) 0.83 (0.68,0.94) 1.09 (0.85,1.37) Q3 1.21n 1.0519 1.94 1.07 Min Max 19 0.11 1.37 1.3719 0.56 2.23 Q119 0.71 0.67 2.14 0.90 0.52 Median 0.97 0.82 (95% (0.71,1.15) CI) 1.06 0.77 (0.94,1.30) 1.11 (0.85,1.66) 0.90 (0.78,1.35) Q3 1.29n 1.4819 2.43 1.70 Min Max 0.26 2.86 1.44 2.90 Q1 0.76 2.81 Median 1.00 (95% (0.76,1.14) CI) Q3 1.15 1.40 Max Table 14: Table 13: Table 15: Table 12: Study Visit Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1

Conﬁdential/Proprietary Information -18- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined n35 Min35 0.6435 0.24 Q1 0.88 0.53 0.79 Median 1.04 0.82 (95% (0.93,1.22) CI) 0.94 (0.84,1.13) 0.94 (0.84,1.06)n Q3 1.2834 1.30 Min35 0.43 2.77 1.14 Max 35 0.15 2.84 Q135 0.76 0.28 2.60 0.78 0.34 Median 0.93 0.78 (95% (0.81,1.18) CI) 0.98 0.68 (0.83,1.12) 0.96 (0.91,1.14) 1.00 (0.88,1.14) Q3 1.32n 1.3734 1350 1.30 Min Max 35 0.65 720 1.3635 0.65 1290 Q135 0.98 0.24 810 1.06 0.49 Median 1.17 0.91 (95% (1.01,1.30) CI) 1.31 0.97 (1.11,1.49) 1.05 (0.93,1.15) 1.09 (0.98,1.14) Q3 1.40 1.59 2.01 1.31n Max 3.88 1.2734 Min 7.21 35 0.24 3.77 35 0.32 Q135 0.67 0.31 0.73 0.33 Median 0.86 0.68 (95% (0.77,0.97) CI) 0.81 0.70 (0.76,0.97) 0.86 (0.80,1.01) 0.90 (0.79,1.04) Q3 1.01n 1.0034 1.53 1.03 Min Max 35 0.79 1.98 1.1235 0.71 2.59 Q135 0.99 0.70 1.87 0.98 0.57 Median 1.12 0.91 (95% (1.02,1.26) CI) 1.14 1.04 (1.03,1.22) 1.11 (0.96,1.24) 1.10 (1.06,1.25) Q3 1.32 1.29 2.36 1.32 Max 1.62 1.41 1.99 3.04 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n16 Min16 0.6416 0.24 Q1 0.90 0.53 0.76 Median 1.04 0.89 (95% (0.93,1.22) CI) 0.89 (0.77,1.02) 0.98 (0.87,1.13)n Q3 1.2415 1.02 Min16 0.50 1.45 1.14 Max 16 0.20 2.54 Q116 0.78 0.28 2.60 0.79 0.34 Median 0.92 0.79 (95% (0.79,1.65) CI) 0.88 0.83 (0.79,1.15) 1.00 (0.80,1.17) 0.96 (0.79,1.18) Q3 1.56n 1.2415 1350 1.17 Min Max 16 0.65 720 1.1816 0.88 1290 Q116 1.04 0.24 810 1.07 0.51 Median 1.14 0.86 (95% (1.01,1.32) CI) 1.37 0.97 (1.06,1.63) 1.02 (0.88,1.14) 1.08 (0.97,1.26) Q3 1.29 1.59 1.50 1.14n Max 2.58 1.1915 Min 7.21 16 0.47 3.77 16 0.58 Q116 0.75 0.59 0.77 0.51 Median 0.90 0.75 (95% (0.77,1.01) CI) 0.95 0.81 (0.78,1.14) 0.87 (0.75,1.01) 1.00 (0.79,1.18) Q3 1.01n 1.1415 1.32 1.02 Min Max 16 0.93 1.98 1.2116 0.75 1.84 Q116 1.00 0.70 1.45 1.02 0.57 Median 1.11 0.88 (95% (0.99,1.15) CI) 1.15 1.00 (1.03,1.22) 1.00 (0.89,1.24) 1.06 (1.00,1.50) Q3 1.21 1.22 1.78 1.25 Max 1.40 1.56 1.57 1.85 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of percent B-cells (CD69 high) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent T-cells (CD4+ HLA-DR+) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent T-cells (CD4+-CD69 high) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of percent natural killer cells (CD56 dim CD16- CD69 high) of live PBMCs fold change from baseline by n19 Min19 0.7419 0.66 Q1 0.88 0.58 0.82 Median 1.07 0.82 (95% (0.89,1.26) CI) 1.09 (0.84,1.33) 0.92 (0.83,1.06)n Q3 1.2919 1.36 Min19 0.43 2.77 1.12 Max 19 0.15 2.84 Q119 0.74 0.33 1.79 0.79 0.46 Median 0.95 0.78 (95% (0.76,1.20) CI) 1.07 0.67 (0.83,1.37) 0.95 (0.81,1.41) 1.08 (0.71,1.41) Q3 1.25n 1.3719 1.96 1.50 Min Max 19 0.67 2.14 1.4319 0.65 2.22 Q119 0.96 0.43 2.12 1.06 0.49 Median 1.21 0.92 (95% (0.96,1.51) CI) 1.31 0.97 (1.10,1.56) 1.08 (0.93,1.57) 1.09 (0.98,1.25) Q3 1.54 1.59 2.01 1.59n Max 3.88 1.2719 Min 6.05 19 0.24 2.12 19 0.32 Q119 0.66 0.31 0.64 0.33 Median 0.85 0.62 (95% (0.66,0.98) CI) 0.78 0.68 (0.64,0.84) 0.86 (0.69,1.01) 0.81 (0.73,1.01) Q3 1.04n 0.8619 1.53 1.03 Min Max 19 0.79 1.76 1.0619 0.71 2.59 Q119 0.99 0.78 1.87 0.94 0.91 Median 1.17 0.94 (95% (0.99,1.34) CI) 1.13 1.07 (0.97,1.31) 1.22 (0.96,1.40) 1.17 (1.08,1.25) Q3 1.34 1.32 2.36 1.43 Max 1.62 1.27 1.99 3.04 Table 19: Descriptive summary statistics of percent natural killer cells (CD56 bright CD69 high) of live PBMCs fold change from baseline by treatment. Table 20: Table 16: Table 17: Table 18: treatment. Study Visit Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Confidential/Proprietary Information -19- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n Minn Q134 Min35 0.55 Median (95% CI)35 0.47 Q135 1.04 0.63 0.90 0.52 Median 1.11 0.98 (95% Q3 (1.06,1.20) CI) 1.10 1.07 (1.01,1.25) 1.41 (1.08,1.74) Max 1.65 (1.22,1.98) Q3 1.28n 1.2934 1.85 1.86 Min Max 35 0.26 2.00 2.2735 0.41 4.58 Q135 0.83 0.00 12.09 0.92 0.12 Median 0.90 0.80 (95% (0.85,1.05) CI) 1.10 0.90 (0.98,1.15) 0.96 (0.84,1.13) 0.96 (0.90,1.05) Q3 1.07n 1.2034 1.77 1.18 Min Max 35 0.47 1.52 1.0835 0.64 1.74 Q135 0.90 0.36 2.89 0.84 0.68 Median 0.96 0.81 (95% (0.92,1.02) CI) 1.00 0.85 (0.90,1.06) 0.92 (0.86,1.01) 1.00 (0.90,1.05) Q3 1.07n 1.0734 1.90 1.08 Min Max 35 0.01 1.26 1.0835 0.03 1.65 Q135 0.78 0.03 1.41 0.96 0.01 Median 0.85 0.81 (95% (0.80,0.99) CI) 1.08 0.81 (1.00,1.19) 0.98 (0.89,1.05) 0.94 (0.86,1.00) Q3 1.12n 1.2434 1.78 1.09 Min Max 35 0.62 1.47 1.0535 0.68 1.84 Q135 0.85 0.66 79.70 0.86 0.70 Median 0.93 0.79 (95% (0.88,0.99) CI) 0.95 0.79 (0.89,1.01) 0.86 (0.84,0.91) 0.85 (0.82,0.90) Q3 1.02 1.04 1.24 0.94 Max 1.55 0.95 1.53 1.22 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n Minn Q115 Min16 0.77 Median (95% CI)16 0.74 Q116 1.04 0.63 0.97 0.53 Median 1.11 0.84 (95% Q3 (1.03,1.20) CI) 1.05 0.98 (1.00,1.28) 1.20 (0.89,1.74) Max 1.68 (1.01,2.25) Q3 1.21n 1.2915 1.46 1.81 Min Max 16 0.77 2.00 2.2616 0.41 3.50 Q116 0.85 0.00 5.17 0.93 0.12 Median 0.92 0.78 (95% (0.85,1.17) CI) 1.09 0.90 (0.93,1.22) 0.94 (0.78,1.19) 0.95 (0.90,1.07) Q3 1.12n 1.2315 1.77 1.19 Min Max 16 0.76 1.41 1.0716 0.64 1.74 Q116 0.92 0.50 1.31 0.95 0.70 Median 1.00 0.84 (95% (0.91,1.12) CI) 1.06 0.85 (0.96,1.10) 1.01 (0.86,1.13) 1.01 (0.85,1.09) Q3 1.12n 1.1115 1.90 1.13 Min Max 16 0.71 1.26 1.1016 0.03 1.65 Q116 0.79 0.03 1.41 0.92 0.01 Median 0.83 0.72 (95% (0.79,1.14) CI) 1.01 0.82 (0.95,1.22) 0.92 (0.72,1.09) 0.94 (0.86,0.98) Q3 1.08n 1.2215 1.78 1.09 Min Max 16 0.62 1.38 0.9816 0.74 1.58 Q116 0.81 0.66 1.28 0.85 0.73 Median 0.92 0.80 (95% (0.81,1.02) CI) 0.93 0.79 (0.85,1.00) 0.88 (0.81,0.93) 0.82 (0.79,0.88) Q3 1.01 1.00 1.12 0.93 Max 1.22 0.87 1.07 1.22 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of percent T-cells (CD4- HLA-DR+) of live PBMCs fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CD86-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CCR5-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CD16- CD86-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CD16+ CD86-) mean fluorescence intensity fold change from baseline by treatment. n Minn Q119 Min19 0.55 Median (95% CI)19 0.47 Q119 1.04 0.81 0.90 0.52 Median 1.12 1.07 (95% Q3 (1.04,1.29) CI) 1.15 1.09 (0.90,1.29) 1.48 (1.11,1.85) Max 1.65 (1.10,1.98) Q3 1.31n 1.2919 1.85 1.86 Min Max 19 0.26 1.63 2.2419 0.64 4.58 Q119 0.73 0.02 12.09 0.90 0.59 Median 0.89 0.85 (95% (0.73,1.06) CI) 1.10 0.87 (0.97,1.15) 0.99 (0.85,1.13) 0.96 (0.90,1.08) Q3 1.06n 1.1619 1.39 1.15 Min Max 19 0.47 1.52 1.0819 0.69 1.32 Q119 0.89 0.36 2.89 0.80 0.68 Median 0.93 0.80 (95% (0.90,1.00) CI) 0.92 0.88 (0.80,1.00) 0.91 (0.82,1.01) 0.96 (0.90,1.04) Q3 1.01n 1.0019 1.12 1.01 Min Max 19 0.01 1.15 1.0419 0.62 1.19 Q119 0.75 0.54 1.31 1.00 0.22 Median 0.88 0.88 (95% (0.78,1.05) CI) 1.11 0.81 (1.00,1.24) 1.00 (0.90,1.05) 0.98 (0.86,1.05) Q3 1.11n 1.2419 1.41 1.07 Min Max 19 0.76 1.47 1.0619 0.68 1.84 Q119 0.90 0.67 79.70 0.88 0.70 Median 0.95 0.79 (95% (0.90,1.02) CI) 0.95 0.81 (0.89,1.10) 0.85 (0.79,0.93) 0.89 (0.84,1.04) Q3 1.02 1.11 1.24 0.94 Max 1.55 1.06 1.53 1.18 Table 21: Table 22: Table 25: Table 24: Table 23: Study Visit Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Confidential/Proprietary Information -20- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n34 Min35 0.7635 0.78 Q135 0.94 0.74 0.96 0.84 Median 1.00 0.90 (95% (0.96,1.04) CI) 1.01 0.92 (0.97,1.09) 0.96 (0.91,1.01) 0.98 (0.93,1.01) Q3 1.08n 1.1134 1.20 1.04 Min Max 35 0.62 1.52 1.0435 0.66 1.36 Q135 0.84 0.65 1.28 0.86 0.68 Median 0.93 0.78 (95% (0.88,1.00) CI) 0.94 0.79 (0.89,1.03) 0.89 (0.82,0.91) 0.85 (0.82,0.92) Q3 1.03n 1.0534 1.27 0.94 Min Max 35 0.66 1.57 0.9635 0.80 1.55 Q135 0.90 0.78 1.24 0.90 0.81 Median 0.94 0.87 (95% (0.92,0.99) CI) 0.93 0.91 (0.91,0.98) 0.94 (0.88,1.00) 0.97 (0.94,1.01) Q3 1.02n 1.0134 1.38 1.02 Min Max 35 0.78 1.13 1.0235 0.84 1.31 Q135 0.91 0.62 1.20 0.93 0.82 Median 0.95 0.90 (95% (0.93,1.01) CI) 0.95 0.93 (0.94,0.98) 0.95 (0.92,1.00) 0.97 (0.94,0.99) Q3 1.04n 1.0334 1.28 1.04 Min Max 35 0.68 1.12 1.0135 0.76 1.33 Q135 0.89 0.73 1.19 0.88 0.80 Median 0.94 0.85 (95% (0.92,0.99) CI) 0.95 0.91 (0.90,0.98) 0.93 (0.89,0.97) 0.96 (0.93,1.00) Q3 1.03n 1.0134 1.29 1.02 Min Max 0.74 1.18 1.05 1.50 Q1 0.89 1.40 Median 0.96 (95% (0.95,0.99) CI) Q3 1.01 1.30 Max USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n15 Min16 0.7616 0.78 Q116 0.90 0.74 0.94 0.87 Median 0.97 0.89 (95% (0.89,1.09) CI) 0.99 0.91 (0.94,1.10) 0.94 (0.88,1.02) 0.96 (0.91,1.01) Q3 1.09n 1.1015 1.20 1.03 Min Max 16 0.62 1.33 1.0016 0.76 1.27 Q116 0.79 0.65 1.22 0.84 0.72 Median 0.91 0.82 (95% (0.80,1.01) CI) 0.93 0.80 (0.84,1.01) 0.90 (0.82,0.94) 0.83 (0.81,0.90) Q3 1.01n 1.0115 1.11 0.94 Min Max 16 0.84 1.21 0.9016 0.80 1.09 Q116 0.90 0.78 1.24 0.91 0.83 Median 0.99 0.90 (95% (0.92,1.05) CI) 0.93 0.89 (0.91,1.01) 0.94 (0.89,1.00) 0.96 (0.89,1.00) Q3 1.05n 1.0115 1.38 1.00 Min Max 16 0.80 1.13 1.0116 0.84 1.31 Q116 0.89 0.77 1.18 0.92 0.82 Median 1.01 0.90 (95% (0.89,1.04) CI) 0.95 0.92 (0.91,1.03) 0.93 (0.92,1.04) 0.96 (0.93,0.99) Q3 1.06n 1.0315 1.28 1.04 Min Max 16 0.82 1.10 0.9916 0.76 1.33 Q116 0.89 0.73 1.11 0.89 0.80 Median 0.96 0.84 (95% (0.90,1.08) CI) 0.95 0.91 (0.89,1.00) 0.93 (0.84,0.96) 0.96 (0.91,1.02) Q3 1.06n 0.9915 1.29 0.97 Min Max 0.74 1.18 1.02 1.50 Q1 0.87 1.32 Median 0.96 (95% (0.86,1.05) CI) Q3 1.06 1.30 Max DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of T-cells (CCR5-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of T-cells (CD4- CCR5-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of T-cells (CD4+ CCR5-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CD16- CCR5-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CD16+ CCR5-) mean fluorescence intensity fold change from baseline by treatment. n19 Min19 0.9119 0.92 Q119 0.96 0.88 0.98 0.84 Median 1.02 0.92 (95% (0.96,1.06) CI) 1.03 0.93 (1.00,1.11) 0.98 (0.93,1.03) 0.99 (0.94,1.04) Q3 1.06n 1.1219 1.18 1.04 Min Max 19 0.74 1.52 1.0719 0.66 1.36 Q119 0.88 0.66 1.28 0.87 0.68 Median 0.94 0.76 (95% (0.88,1.03) CI) 0.96 0.79 (0.87,1.13) 0.85 (0.76,0.92) 0.91 (0.82,1.05) Q3 1.04n 1.1519 1.27 0.93 Min Max 19 0.66 1.57 1.0519 0.80 1.55 Q119 0.91 0.78 1.17 0.90 0.81 Median 0.94 0.87 (95% (0.91,0.97) CI) 0.93 0.91 (0.90,1.00) 0.93 (0.87,1.02) 0.99 (0.91,1.04) Q3 0.97n 1.0419 1.14 1.03 Min Max 19 0.78 1.09 1.0619 0.86 1.14 Q119 0.92 0.62 1.20 0.93 0.86 Median 0.95 0.90 (95% (0.93,0.97) CI) 0.95 0.94 (0.93,1.01) 0.95 (0.91,1.02) 0.98 (0.94,1.02) Q3 0.98n 1.0319 1.13 1.03 Min Max 19 0.68 1.12 1.0419 0.78 1.07 Q119 0.89 0.79 1.19 0.88 0.84 Median 0.94 0.87 (95% (0.89,0.98) CI) 0.95 0.92 (0.88,0.99) 0.93 (0.89,1.06) 0.98 (0.92,1.08) Q3 0.99n 1.0219 1.14 1.06 Min Max 0.75 1.14 1.09 1.22 Q1 0.94 1.40 Median 0.96 (95% (0.95,0.99) CI) Q3 1.00 1.22 Max Table 28: Table 30: Table 29: Table 27: Table 26: Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1

Confidential/Proprietary Information -21- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined n35 Min35 0.6635 0.68 Q1 0.92 0.69 0.89 Median 0.97 0.91 (95% (0.94,1.00) CI) 0.92 (0.90,1.00) 0.96 (0.93,1.00) Q3 1.02 1.02n 1.22 1.0534 Max Min 1.26 35 0.73 1.29 35 0.70 Q135 0.89 0.61 0.88 0.72 Median 0.97 0.88 (95% (0.92,1.03) CI) 1.00 0.86 (0.92,1.04) 0.98 (0.90,1.04) 0.95 (0.88,0.97) Q3 1.06 1.06 1.17 1.07n Max 1.36 1.0134 Min 1.25 35 0.72 1.42 35 0.62 Q135 0.93 0.68 0.93 0.66 Median 0.97 0.87 (95% (0.94,1.01) CI) 0.96 0.92 (0.93,1.03) 0.94 (0.89,0.98) 0.97 (0.93,1.00) Q3 1.05 1.04 1.36 1.02n Max 1.25 1.0534 Min 1.31 35 0.73 1.26 35 0.68 Q135 0.87 0.48 0.86 0.65 Median 0.95 0.86 (95% (0.87,0.98) CI) 0.98 0.84 (0.95,1.06) 0.96 (0.89,1.03) 0.91 (0.86,1.02) Q3 1.02n 1.1434 1.78 1.08 Min Max 35 0.23 2.29 1.0735 0.59 3.32 Q135 0.78 0.29 2.14 0.82 0.08 Median 0.87 0.81 (95% (0.81,0.97) CI) 0.93 0.84 (0.87,1.02) 0.91 (0.85,0.99) 0.99 (0.94,1.04) Q3 1.00 1.05 1.36 1.05 Max 1.56 1.17 1.99 1.89 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n16 Min16 0.6616 0.68 Q1 0.89 0.70 0.85 Median 0.97 0.89 (95% (0.88,1.02) CI) 0.94 (0.85,1.03) 0.94 (0.90,0.99) Q3 1.03 1.03n 1.17 0.9915 Max Min 1.19 16 0.73 1.08 16 0.70 Q116 0.81 0.68 0.85 0.72 Median 0.94 0.82 (95% (0.79,1.07) CI) 0.94 0.82 (0.85,1.06) 0.97 (0.83,1.06) 0.86 (0.83,0.95) Q3 1.07 1.06 1.16 1.07n Max 1.36 0.9515 Min 1.25 16 0.74 1.19 16 0.62 Q116 0.89 0.68 0.91 0.66 Median 0.97 0.84 (95% (0.86,1.06) CI) 0.96 0.90 (0.90,1.04) 0.92 (0.84,1.05) 0.95 (0.91,0.98) Q3 1.06 1.05 1.36 1.06n Max 1.19 0.9915 Min 1.25 16 0.77 1.19 16 0.68 Q116 0.86 0.48 0.86 0.65 Median 0.92 0.80 (95% (0.86,1.06) CI) 0.96 0.86 (0.86,1.04) 0.96 (0.83,1.07) 0.95 (0.86,1.07) Q3 1.03n 1.0515 1.27 1.07 Min Max 16 0.23 1.35 1.0816 0.59 1.49 Q116 0.76 0.29 1.48 0.84 0.08 Median 0.87 0.72 (95% (0.74,1.00) CI) 0.95 0.86 (0.83,1.03) 0.90 (0.72,1.06) 1.00 (0.90,1.03) Q3 1.02 1.03 1.36 1.06 Max 1.56 1.03 1.99 1.89 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of T-cells (CD4- CD69-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of natural killer cells (CD56 bright CD69-) mean fluorescence intensity fold change from baseline by Descriptive summary statistics of natural killer cells (CD56 bright CCR5-) mean fluorescence intensity fold change from baseline by n19 Min19 0.7419 0.81 Q1 0.94 0.69 0.90 Median 0.97 0.94 (95% (0.94,1.01) CI) 0.92 (0.90,1.00) 0.98 (0.96,1.07) Q3 1.02 1.01n 1.22 1.1019 Max Min 1.26 19 0.78 1.29 19 0.75 Q119 0.92 0.61 0.95 0.77 Median 1.01 0.91 (95% (0.92,1.04) CI) 1.01 0.91 (0.95,1.06) 0.98 (0.93,1.05) 0.99 (0.92,1.09) Q3 1.04 1.09 1.17 1.07n Max 1.25 1.0919 Min 1.14 19 0.72 1.42 19 0.72 Q119 0.94 0.79 0.93 0.66 Median 0.96 0.90 (95% (0.94,1.01) CI) 0.96 0.93 (0.93,1.03) 0.94 (0.92,1.00) 1.00 (0.93,1.11) Q3 1.01 1.03 1.23 1.00n Max 1.25 1.1219 Min 1.31 19 0.73 1.26 19 0.73 Q119 0.87 0.84 0.89 0.69 Median 0.96 0.89 (95% (0.87,1.00) CI) 1.01 0.84 (0.94,1.16) 0.96 (0.89,1.02) 0.91 (0.85,0.99) Q3 1.01n 1.2319 1.78 1.07 Min Max 19 0.67 2.29 1.0319 0.73 3.32 Q119 0.78 0.67 2.14 0.82 0.57 Median 0.87 0.84 (95% (0.78,0.98) CI) 0.91 0.84 (0.84,1.08) 0.91 (0.85,0.99) 0.99 (0.84,1.19) Q3 0.99 1.09 1.17 1.02 Max 1.50 1.20 1.72 1.54 Descriptive summary statistics of natural killer cells (CD56 bright CD16+ CCR5-) mean fluorescence intensity fold change from baseline Descriptive summary statistics of natural killer cells (CD56 bright CD16- CCR5-) mean fluorescence intensity fold change from baseline by Table 34: treatment. Table 31: Table 32: by treatment. Table 33: Table 35: treatment. treatment. Study Visit Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Confidential/Proprietary Information -22- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined n34 Min35 0.2135 0.30 Q135 0.65 0.06 0.85 0.18 Median 0.89 0.73 (95% (0.75,0.96) CI) 1.10 0.83 (0.94,1.27) 0.99 (0.78,1.16) 1.04 (0.91,1.21) Q3 1.08 1.45 2.25 1.29n Max 3.25 1.2934 Min 3.62 35 0.54 2.76 35 0.56 Q135 0.81 0.39 0.83 0.04 Median 0.87 0.79 (95% (0.83,0.99) CI) 0.90 0.79 (0.86,0.96) 0.88 (0.82,0.97) 0.97 (0.87,1.07) Q3 1.01 1.02 1.40 1.06n Max 1.62 1.1734 Min 2.23 35 0.08 2.02 35 0.57 Q135 0.88 0.50 1.00 0.24 Median 1.05 0.94 (95% (0.93,1.09) CI) 1.15 0.90 (1.02,1.25) 0.99 (0.95,1.07) 1.08 (0.94,1.15) Q3 1.12 1.31 1.83 1.21n Max 2.21 1.2034 Min 3.70 35 0.51 2.00 35 0.34 Q135 0.79 0.50 0.78 0.69 Median 0.94 0.74 (95% (0.84,1.02) CI) 0.92 0.85 (0.82,0.99) 0.90 (0.79,1.03) 0.95 (0.92,1.05) Q3 1.04n 1.0634 2.43 1.10 Min Max 35 0.75 2.90 1.1135 0.63 2.86 Q135 0.93 0.07 2.58 0.95 0.54 Median 1.01 0.85 (95% (0.96,1.04) CI) 1.03 0.84 (0.96,1.09) 0.94 (0.88,1.00) 0.93 (0.86,1.02) Q3 1.06 1.12 1.24 1.04 Max 1.82 1.05 3.47 1.56 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n15 Min16 0.2116 0.30 Q116 0.72 0.06 0.82 0.21 Median 0.95 0.64 (95% (0.79,1.12) CI) 1.21 0.85 (0.83,1.46) 1.01 (0.65,1.33) 1.02 (0.89,1.29) Q3 1.12 1.46 1.99 1.34n Max 1.81 1.3015 Min 3.62 16 0.54 1.65 16 0.59 Q116 0.82 0.39 0.84 0.04 Median 0.85 0.70 (95% (0.82,0.98) CI) 0.90 0.78 (0.84,0.95) 0.88 (0.70,1.08) 0.96 (0.80,1.07) Q3 1.00 0.95 1.40 1.09n Max 1.62 1.0715 Min 2.23 16 0.08 2.02 16 0.57 Q116 0.86 0.50 0.96 0.24 Median 0.99 0.91 (95% (0.88,1.11) CI) 1.14 0.91 (0.95,1.27) 0.96 (0.91,1.13) 0.99 (0.92,1.14) Q3 1.10 1.27 1.83 1.16n Max 1.93 1.1215 Min 2.06 16 0.71 1.57 16 0.65 Q116 0.82 0.55 0.89 0.69 Median 0.91 0.79 (95% (0.83,1.03) CI) 0.96 0.90 (0.90,1.10) 0.96 (0.79,1.08) 1.07 (0.91,1.12) Q3 1.03n 1.1115 2.43 1.08 Min Max 16 0.75 2.90 1.1216 0.77 2.86 Q116 0.89 0.07 2.58 0.89 0.72 Median 0.96 0.81 (95% (0.91,1.04) CI) 0.97 0.75 (0.90,1.09) 0.88 (0.80,0.94) 0.85 (0.75,0.92) Q3 1.04 1.09 1.10 0.94 Max 1.52 0.92 1.36 1.24 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of B-cells (CD69-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (HLA-DR) mean fluorescence intensity fold change from baseline by treatment. n19 Min19 0.3319 0.37 Q119 0.63 0.35 0.85 0.18 Median 0.84 0.80 (95% (0.65,0.94) CI) 1.09 0.83 (0.85,1.26) 0.99 (0.83,1.21) 1.08 (0.84,1.21) Q3 0.96 1.26 2.25 1.23n Max 3.25 1.2519 Min 3.44 19 0.74 2.76 19 0.56 Q119 0.80 0.64 0.81 0.53 Median 0.88 0.84 (95% (0.80,1.00) CI) 0.89 0.82 (0.84,1.04) 0.88 (0.85,0.98) 0.98 (0.87,1.17) Q3 1.01 1.05 1.12 1.01n Max 1.48 1.1919 Min 1.59 19 0.64 1.43 19 0.73 Q119 0.90 0.57 1.00 0.55 Median 1.06 0.95 (95% (0.93,1.13) CI) 1.15 0.91 (1.00,1.30) 1.05 (0.95,1.17) 1.10 (0.94,1.23) Q3 1.17 1.49 1.83 1.25n Max 2.21 1.2419 Min 3.70 19 0.51 2.00 19 0.34 Q119 0.77 0.50 0.73 0.73 Median 0.94 0.71 (95% (0.77,1.06) CI) 0.82 0.83 (0.77,0.99) 0.90 (0.72,1.09) 0.93 (0.83,1.04) Q3 1.11n 0.9919 1.40 1.13 Min Max 19 0.88 1.96 1.0419 0.63 2.72 Q119 0.99 0.80 2.02 0.98 0.54 Median 1.04 0.92 (95% (1.00,1.09) CI) 1.07 0.93 (0.99,1.12) 0.97 (0.94,1.08) 1.00 (0.95,1.10) Q3 1.10 1.30 1.24 1.11 Max 1.82 1.11 3.47 1.56 Descriptive summary statistics of natural killer cells (CD56 dim CD16- CD69-) mean fluorescence intensity fold change from baseline by Descriptive summary statistics of natural killer cells (CD56 bright CD16- CD69-) mean fluorescence intensity fold change from baseline by Descriptive summary statistics of natural killer cells (CD56 bright CD16+ CD69-) mean fluorescence intensity fold change from baseline by Table 39: Table 40: Table 36: treatment. Table 37: treatment. Table 38: treatment. Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Confidential/Proprietary Information -23- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n34 Min35 0.7635 0.76 Q135 0.91 0.21 0.94 0.54 Median 0.99 0.77 (95% (0.95,1.03) CI) 1.03 0.86 (0.95,1.09) 0.90 (0.82,1.07) 0.95 (0.90,1.04) Q3 1.07n 1.1234 1.52 1.12 Min Max 35 0.72 1.96 1.1235 0.62 4.72 Q135 0.94 0.06 2.06 0.95 0.52 Median 1.02 0.86 (95% (0.97,1.05) CI) 1.05 0.84 (0.97,1.13) 0.94 (0.89,1.01) 0.94 (0.87,1.05) Q3 1.07n 1.1440 1.30 1.02 Min Max 40 0.17 1.76 1.0640 0.19 3.36 Q140 0.61 0.24 1.48 0.77 0.14 Median 1.25 0.55 (95% (0.87,1.79) CI) 1.24 0.54 (0.88,1.86) 0.80 (0.70,1.16) 1.08 (0.64,1.64) Q3 1.94n 2.6840 23.39 1.83 Min Max 40 1 14.28 2.3440 1 52.21 Q140 1 50.30 1 1 1 Median (95% CI) 1 1 1 (1,1) 1 (1,1) Q3 1 (1,1)n 1 (1,1)40 Min Max 40 0.2440 0.03 Q1 140 0.74 0.18 1 0.86 0.17 1 Median 1.20 0.56 (95% (0.90,1.45) CI) 1 1 1.21 0.70 (1.00,1.74) 1 0.84 (0.68,1.32) 1 1.07 (0.87,1.34) Q3 1 2.10n 2.2140 5.42 1.70 Min Max 0.38 7.23 1.79 7.82 Q1 1 4.04 Median (95% CI) 1 (1,1) Q3 Max 1 3.77 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n15 Min16 0.7916 0.80 Q116 0.95 0.21 0.93 0.54 Median 0.99 0.75 (95% (0.95,1.08) CI) 1.03 0.76 (0.92,1.12) 0.89 (0.75,1.15) 0.93 (0.77,1.14) Q3 1.11n 1.1115 1.52 1.15 Min Max 16 0.72 1.96 1.1416 0.79 1.73 Q116 0.87 0.06 2.06 0.90 0.64 Median 0.94 0.80 (95% (0.89,1.03) CI) 0.97 0.79 (0.90,1.13) 0.88 (0.79,0.95) 0.85 (0.78,0.90) Q3 1.02n 1.1318 1.15 0.96 Min Max 18 0.17 1.42 0.8918 0.19 1.28 Q118 0.55 0.24 1.16 0.54 0.14 Median 0.93 0.50 (95% (0.56,1.89) CI) 0.90 0.52 (0.67,1.99) 0.75 (0.58,2.09) 0.84 (0.53,2.56) Q3 1.90n 2.3618 23.39 2.20 Min Max 18 1 14.28 2.6918 1 13.90 Q118 1 7.71 1 1 1 Median (95% CI) 1 1 1 (1,1) 1 (1,1) Q3 1 (1,1)n 1 (1,1)18 Min Max 18 0.2418 0.03 Q1 118 0.61 0.29 1 0.76 0.17 1 Median 1.03 0.53 (95% (0.64,1.68) CI) 1 1 1.21 0.44 (0.78,1.96) 1 1.05 (0.54,2.12) 1 1.03 (0.44,1.33) Q3 1 1.77n 2.1418 5.11 2.13 Min Max 0.38 7.23 1.34 5.10 Q1 1 4.04 Median (95% CI) 1 (1,1) Q3 Max 1 3.77 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of Human Interleukin-1 beta concentration fold change from baseline by treatment. Descriptive summary statistics of Human platelet-derived growth factor concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-1 receptor antagonist concentration fold change from baseline by treatment. Table 44: Descriptive summary statistics of monocyte cells (CD16- HLA-DR) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of monocyte cells (CD16+ HLA-DR) mean fluorescence intensity fold change from baseline by treatment. n19 Min19 0.7619 0.76 Q119 0.90 0.68 0.94 0.71 Median 0.97 0.86 (95% (0.91,1.04) CI) 1.03 0.90 (0.94,1.10) 0.95 (0.90,1.09) 0.96 (0.90,1.04) Q3 1.05n 1.1419 1.29 1.10 Min Max 19 0.92 1.46 1.0719 0.62 4.72 Q119 0.99 0.80 1.35 1.02 0.52 Median 1.04 0.91 (95% (1.00,1.07) CI) 1.08 0.96 (1.02,1.15) 0.98 (0.91,1.08) 1.01 (0.97,1.11) Q3 1.09n 1.3122 1.30 1.11 Min Max 22 0.22 1.76 1.1222 0.23 3.36 Q122 0.91 0.33 1.48 0.89 0.15 Median 1.58 0.60 (95% (1.00,1.86) CI) 1.66 0.60 (1.07,2.50) 0.85 (0.70,1.16) 1.28 (0.71,1.86) Q3 1.97n 2.7922 5.05 1.47 Min Max 22 1 6.18 2.1522 1 52.21 Q122 1 50.30 1 1 1 Median (95% CI) 1 1 1 (1,1) 1 (1,1) Q3 1 (1,1)n 1 (1,1)22 Min Max 22 0.5422 0.30 Q1 122 0.89 0.18 1 0.95 0.27 1 Median 1.23 0.58 (95% (0.94,2.09) CI) 1 1 1.28 0.81 (1.01,2.08) 1 0.80 (0.64,1.16) 1 1.12 (0.87,1.66) Q3 1 2.26n 2.1722 5.42 1.30 Min Max 0.68 4.01 1.87 7.82 Q1 1 3.61 Median (95% CI) 1 (1,1) Q3 Max 1 1.45 Table 43: Table 45: Table 42: Table 41: Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1

Conﬁdential/Proprietary Information -24- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n40 Min40 0.3840 0.32 Q1 1 0.32 1 Median 1 (95% CI) 1 (1,1) 1 (1,1) 1 (1,1)n Q340 Min40 0.35 Max 40 0.35 Q1 140 0.93 0.22 1 0.98 0.18 1 Median 1.00 0.46 (95% (1.00,1.27) CI) 3.67 1.12 0.90 (1.00,1.38) 3.64 0.96 (0.57,1.00) 3.95 1.00 (0.95,1.13) Q3 1.54n 1.9340 5.32 1.27 Min Max 40 0.65 4.93 1.5840 0.32 4.36 Q140 1 0.32 3.61 1 0.32 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1)n40 Min Max 40 0.41 140 0.41 Q1 140 1 0.41 1 1 0.41 2.71 1 Median 1 (95% CI) 1.00 1 1 (1,1) 1.00 1 (1,1) 2.03 1 (1,1) Q3 1 (1,1)n40 Min Max 40 1 140 1 Q1 140 1 1 1 1 4.68 1 1 Median (95% CI) 5.18 1 4.48 1 1 (1,1) 4.33 1 (1,1) Q3 1 (1,1)n 1 (1,1)40 Min Max 1.00 Q1 1 1 1 1 Median (95% CI) 3.38 1 1 (1,1) 2.02 2.05 Q3 1.00 Max 1 2.98 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n18 Min18 0.3818 0.38 Q1 1 0.38 1 Median 1 (95% CI) 1 (1,1) 1 (1,1) 1 (1,1)n Q318 Min18 0.35 Max 18 0.35 Q1 118 0.51 0.25 1 0.79 0.18 1 Median 1.00 0.47 (95% (0.56,1.16) CI) 3.67 1.14 0.65 (0.81,2.06) 3.64 0.84 (0.49,1.80) 3.44 0.98 (0.67,1.26) Q3 1.22n 2.0618 5.32 2.02 Min Max 18 0.73 4.93 1.2818 0.32 3.02 Q118 1 0.32 3.39 1 0.32 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1)n18 Min Max 18 0.41 118 0.41 Q1 118 1 0.41 1 1 0.41 1 1 Median 1 (95% CI) 1 1 1 (1,1) 1 1 (1,1) 1 1 (1,1) Q3 1 (1,1)n18 Min Max 18 1 118 1 Q1 118 1 1 1 1 4.68 1 1 Median (95% CI) 5.18 1 4.48 1 1 (1,1) 4.33 1 (1,1) Q3 1 (1,1)n 1 (1,1)18 Min Max 1 Q1 1 1 1 1 Median (95% CI) 1.00 1 2.02 1 (1,1) 1.00 Q3 1.00 Max 1 1 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of Human Interleukin-2 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-4 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-5 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-6 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-7 concentration fold change from baseline by treatment. Table 46: Table 47: Table 48: Table 49: Table 50: n22 Min22 0.4122 0.32 Q1 1 0.32 1 Median 1 (95% CI) 1 (1,1) 1 (1,1) 1 (1,1)n Q322 Min22 0.44 Max 22 0.73 Q1 122 1.00 0.22 1 1.00 0.34 1 Median 1.12 0.45 (95% (1.00,1.61) CI) 1.09 1.12 0.95 (1.01,1.75) 1.18 0.96 (0.54,1.00) 3.95 1.00 (0.96,1.38) Q3 1.72n 1.7622 3.61 1.00 Min Max 22 0.65 3.41 1.5922 0.44 4.36 Q122 1 0.60 3.61 1 0.76 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1)n22 Min Max 22 1 122 1 Q1 122 1 1 1 1 2.71 1 1 Median (95% CI) 1.00 1 1.00 1 1 (1,1) 2.03 1 (1,1) Q3 1 (1,1)n 1 (1,1)22 Min Max 22 122 1 Q1 122 1 1 1 1 1 1 Median (95% CI) 3.82 1 1 1.00 1 1 (1,1) 2.29 1 (1,1) Q3 1.00 1 (1,1)n 1 (1,1)22 Min Max 1.00 Q1 1 1 1 1 Median (95% CI) 3.38 1 1 (1,1) 1.00 2.05 Q3 1.00 Max 1 2.98 Study Visit Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1

Conﬁdential/Proprietary Information -25- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined n40 Min40 0.4540 0.97 Q1 1 0.45 1 Median 1 (95% CI) 1 (1,1) 1 (1,1) 1 (1,1)n Q340 Min40 0.03 Max 40 0.03 Q1 140 1 0.03 1 1 0.03 1 Median 1 (95% CI) 2.31 1 1 (1,1) 2.25 1 (1,1) 2.38 1 (1,1) Q3 1 (1,1)n40 Min Max 40 0.32 140 0.32 Q1 140 1 0.32 1 1 0.32 16.96 1 Median 1 (95% CI) 29.37 1 1 (1,1) 35.55 1 (1,1) 32.64 1 (1,1) Q3 1 (1,1)n40 Min Max 40 0.30 140 0.35 Q1 140 1 0.35 1 1 0.24 1.30 1 Median 1 (95% CI) 2.17 1 1 (1,1) 2.40 1 (1,1) 2.74 1 (1,1) Q3 1 (1,1)n Max 40 Min 140 0.34 140 0.40 1 Q140 1 0.40 3.09 1 1 0.40 2.23 Median 1 (95% CI) 2.83 1 1 (1,1) 5.58 1 (1,1) 1 (1,1) Q3 1 (1,1) Max 1 1 1 5.53 1 3.72 2.80 5.17 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n18 Min18 118 1 Q1 1 1 1 Median (95% CI) 1 1 (1,1) 1 (1,1)n Q3 1 (1,1)18 Min18 0.16 Max 18 0.06 Q118 0.90 0.16 1 1.00 0.06 1 Median 1 0.84 (95% (0.94,1) CI) 1 1 1.00 (1.00,1) 1 1 (0.90,1) 1 1 (1.00,1) Q3 1 n18 1.00 Min Max 18 0.45 1.0118 0.45 16.96 1.00 Q118 1 0.45 29.37 1.00 1 0.45 6.30 Median 1 21.38 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1)n18 Min Max 18 0.30 118 0.50 Q1 118 1 0.53 1 1 0.24 1.00 1 Median 1 (95% CI) 2.17 1 1 (1,1) 1.00 1 (1,1) 1.00 1 (1,1) Q3 1 (1,1)n Max 18 Min 118 0.34 118 0.40 1 Q118 0.96 0.40 3.09 1 0.99 0.40 2.02 Median 1 1.00 (95% (0.98,1) CI) 2.01 1 0.89 (1.00,1) 2.79 1 (1.00,1) 1 (0.92,1) Q3 1 Max 1 1 5.53 1 3.72 2.80 5.17 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of Human Interleukin-8 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-9 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-10 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-13 concentration fold change from baseline by treatment. Table 51: Table 52: Table 53: Table 55: Descriptive summary statistics of Human Interleukin-12 (Lupus Ku autoantigen protein p70) concentration fold change from baseline by n22 Min22 0.4522 0.97 Q1 1 0.45 1 Median 1 (95% CI) 1 (1,1) 1 (1,1) 1 (1,1)n Q322 Min22 0.03 Max 22 0.03 Q1 122 1 0.03 1 1 0.03 1 Median 1 (95% CI) 2.31 1 1 (1,1) 2.25 1 (1,1) 2.38 1 (1,1) Q3 1 (1,1)n22 Min Max 22 0.32 1.0522 0.32 Q1 1.0022 1 0.32 3.60 1.21 1 0.32 16.34 1.00 Median 1 (95% CI) 35.55 1 1 (1,1) 32.64 1 (1,1) 1 (1,1) Q3 1 (1,1)n22 Min Max 22 0.35 122 0.35 Q1 122 1 0.35 1 1 0.35 1.30 1 Median 1 (95% CI) 1.23 1 1 (1,1) 2.40 1 (1,1) 2.74 1 (1,1) Q3 1 (1,1)n Max 22 Min 122 0.61 122 0.43 1 Q122 1 0.44 2.67 1 1 0.69 2.23 Median 1 (95% CI) 2.83 1 1 (1,1) 5.58 1 (1,1) 1 (1,1) Q3 1 (1,1) Max 1 1 1 1.12 1 1.09 1.61 3.16 treatment. Table 54: Study Visit Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Conﬁdential/Proprietary Information -26- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined Combined n Minn Q140 Min40 1 Median (95% CI)40 1 Q140 1 1 1 1 Median (95% Q3 CI) 1 1 1 (1,1) Max 1 (1,1) Q3 1 (1,1)n 1 (1,1)40 Min Max 40 0.2240 0.20 Q1 140 1 0.22 1 1 0.22 1 Median 1 (95% CI) 1 1 1 1 (1,1) 1 1 (1,1) 1 1 (1,1) Q3 1 1 (1,1)n40 Min Max 40 0.03 140 0.02 Q1 140 0.95 0.02 1 0.99 0.03 6.28 1 Median 1 0.88 (95% (1,1.00) CI) 1.16 1 0.80 (1,1.19) 3.88 1 (1,1.00) 15.57 1 (1,1.00) Q3n40 1.08 Min Max 40 0.19 1.7040 0.46 42.59 1.08 Q140 0.93 0.41 58.82 1.42 0.90 0.19 58.53 Median 1.02 0.79 72.17 (95% (1.00,1.22) CI) 1.03 0.89 (0.99,1.28) 1.00 (0.86,1.13) 1.01 (0.97,1.15) Q3 1.50n 1.3940 7.12 1.39 Min Max 40 0.23 5.22 1.4040 0.15 6.46 Q140 1 0.15 3.25 1 0.15 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1) Max 1.92 1.03 4.03 1.00 3.78 1.09 3.80 3.33 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n Minn Q118 Min18 1 Median (95% CI)18 1 Q118 1 1 1 1 Median (95% Q3 CI) 1 1 1 (1,1) Max 1 (1,1) Q3 1 (1,1)n 1 (1,1)18 Min Max 18 0.2418 0.20 Q1 118 1 0.24 1 1 0.30 1 Median 1 (95% CI) 1 1 1 1 (1,1) 1 1 (1,1) 1 1 (1,1) Q3 1 1 (1,1)n18 Min Max 18 0.03 118 0.03 Q1 118 0.76 0.03 1 0.74 0.03 6.28 1 Median 1 0.55 (95% (0.81,1.00) CI) 1.00 1 0.53 (0.76,1.70) 1.00 1 (0.61,1.01) 7.25 1 (0.60,1.00) Q3n 1.0018 2.05 Min Max 18 0.19 42.59 1.0218 0.59 58.82 1.00 Q118 0.80 0.59 13.22 0.75 0.19 40.31 Median 1.00 0.76 (95% (0.88,1.36) CI) 1.00 0.70 (0.78,1.31) 0.98 (0.80,1.60) 0.95 (0.72,1.36) Q3 1.44n 1.3218 7.12 1.62 Min Max 18 0.23 5.22 1.4018 0.15 3.59 Q118 1 0.15 3.25 1 0.15 Median 1 (95% CI) 1 1 (1,1.58) 1 (1,1.00) 1 (1,1.00) Q3 1 (1,1.00) Max 1.88 1.00 3.06 1.00 2.71 1.00 2.84 2.92 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of Human Eotaxin concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-15 concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interleukin-17 concentration fold change from baseline by treatment. Table 58: Descriptive summary statistics of Human basic ﬁbroblast growth factor concentration fold change from baseline by treatment. Table 56: Table 57: Descriptive summary statistics of Human granulocyte-colony stimulating factor concentration fold change from baseline by treatment. n Minn Q122 Min22 1 Median (95% CI)22 1 Q122 1 1 1 1 Median (95% Q3 CI) 1 1 1 (1,1) Max 1 (1,1) Q3 1 (1,1)n 1 (1,1)22 Min Max 22 0.2222 0.22 Q1 122 1 0.22 1 1 0.22 1 Median 1 (95% CI) 1 1 1 1 (1,1) 1 1 (1,1) 1 1 (1,1) Q3 1 1 (1,1)n22 Min Max 22 0.15 122 0.02 Q1 122 1.00 0.02 1 1.00 0.46 2.88 1 Median 1 1.00 (95% (1,1.15) CI) 1.16 1 0.92 (1,1.38) 3.88 1 (1,1.04) 15.57 1 (1,1.40) Q3n22 1.26 Min Max 22 0.46 1.4522 0.46 39.60 1.08 Q122 0.98 0.41 35.34 1.45 0.98 0.29 58.53 Median 1.06 0.80 72.17 (95% (1.00,1.27) CI) 1.12 0.98 (1.00,1.34) 1.00 (0.81,1.15) 1.06 (1.00,1.27) Q3 1.44n 1.5322 4.47 1.23 Min Max 22 0.40 3.75 1.3922 0.91 6.46 Q122 1 0.40 2.71 1 0.24 Median 1 (95% CI) 1 1 (1,1.54) 1 (1,1.18) 1 (1,1.00) Q3 1 (1,1.74) Max 1.84 1.29 4.03 1.00 3.78 2.09 3.80 3.33 Table 59: Table 60: Study Visit Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Conﬁdential/Proprietary Information -27- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined n40 Min40 0.3640 0.14 Q140 0.82 0.14 0.73 0.03 Median 1.05 0.68 (95% (0.94,1.30) CI) 1.04 0.77 (0.90,1.29) 0.92 (0.77,1.09) 1.01 (0.82,1.16) Q3 1.50 1.56 7.71 1.24n Max 7.14 1.7340 Min 20.46 40 0.19 10.94 40 0.03 Q140 0.77 0.09 0.88 0.01 Median 1.21 0.59 (95% (0.89,1.57) CI) 1.27 0.69 (0.95,1.58) 0.82 (0.66,1.23) 1.07 (0.88,1.21) Q3 2.29n 1.9640 5.75 1.63 Min Max 40 0.56 27.75 1.7740 0.54 20.35 Q140 0.81 0.50 16.37 0.88 0.40 Median 1.16 0.84 (95% (1.00,1.32) CI) 1.26 0.78 (1.05,1.60) 0.98 (0.91,1.15) 0.91 (0.82,1.13) Q3 1.49n 2.0340 18.86 1.27 Min Max 40 0.61 4.38 1.2540 0.50 3.18 Q140 0.82 0.35 4.02 0.90 0.29 Median 1.08 0.78 (95% (0.92,1.23) CI) 1.05 0.82 (0.98,1.14) 0.94 (0.86,1.00) 1.00 (0.89,1.11) Q3 1.27 1.21 2.02 1.07n Max 3.86 1.1840 Min 7.90 40 0.34 3.64 40 0.34 Q140 1 0.34 1 0.34 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1) Max 1 1 1 2.47 1 1.00 2.20 2.22 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n18 Min18 0.3618 0.40 Q118 0.65 0.42 0.72 0.39 Median 1.02 0.66 (95% (0.67,1.75) CI) 0.97 0.68 (0.73,1.44) 0.84 (0.67,1.26) 0.90 (0.72,1.70) Q3 1.77 1.58 7.71 1.27n Max 7.14 1.8618 Min 20.46 18 0.19 10.94 18 0.03 Q118 0.44 0.20 0.77 0.01 Median 1.06 0.52 (95% (0.58,1.88) CI) 1.16 0.52 (0.78,1.77) 1.02 (0.56,1.68) 0.94 (0.55,1.50) Q3 2.10n 1.8518 4.54 1.72 Min Max 18 0.65 27.75 1.6318 0.69 20.35 Q118 0.77 0.64 16.37 0.92 0.40 Median 1.14 0.80 (95% (0.78,1.35) CI) 1.43 0.66 (1.02,1.80) 0.98 (0.81,1.20) 0.90 (0.72,1.10) Q3 1.37n 1.8618 18.86 1.22 Min Max 18 0.61 3.21 1.1618 0.50 3.18 Q118 0.78 0.40 4.02 0.75 0.29 Median 0.98 0.71 (95% (0.79,1.15) CI) 1.01 0.81 (0.81,1.10) 0.90 (0.72,1.00) 0.96 (0.82,1.12) Q3 1.20 1.12 1.39 1.00n Max 1.63 1.1318 Min 1.70 18 0.34 1.55 18 0.34 Q118 1 0.34 1 0.34 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1) Max 1 1 1 2.47 1 1.00 1.00 2.22 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of Human interferon gamma concentration fold change from baseline by treatment. Descriptive summary statistics of Human Interferon gamma-induced protein 10 concentration fold change from baseline by treatment. Table 62: Descriptive summary statistics of Human granulocyte macrophage-colony stimulating factor concentration fold change from baseline by n22 Min22 0.4422 0.14 Q122 0.88 0.14 0.82 0.03 Median 1.10 0.76 (95% (0.92,1.35) CI) 1.04 0.81 (0.88,1.51) 0.94 (0.77,1.12) 1.01 (0.88,1.26) Q3 1.42 1.55 2.59 1.14n Max 2.36 1.3422 Min 4.14 22 0.40 2.33 22 0.19 Q122 0.92 0.09 0.92 0.03 Median 1.21 0.62 (95% (0.94,1.86) CI) 1.34 0.87 (1.00,1.69) 0.82 (0.69,1.00) 1.09 (0.95,1.74) Q3 2.17n 1.9822 5.75 1.10 Min Max 22 0.56 5.31 1.8022 0.54 9.71 Q122 0.90 0.50 4.15 0.90 0.51 Median 1.22 0.90 (95% (0.97,1.43) CI) 1.24 0.82 (0.98,2.01) 0.96 (0.91,1.19) 0.97 (0.82,1.24) Q3 1.51n 2.0822 2.07 1.39 Min Max 22 0.70 4.38 1.3022 0.67 3.04 Q122 0.86 0.35 2.83 0.98 0.38 Median 1.20 0.83 (95% (0.94,1.33) CI) 1.08 0.84 (1.02,1.22) 0.96 (0.84,1.07) 1.06 (0.88,1.18) Q3 1.40 1.29 2.02 1.10n Max 3.86 1.2022 Min 7.90 22 1.00 3.64 22 0.98 Q122 1 1.00 1 1.00 Median 1 (95% CI) 1 1 (1,1) 1 (1,1) 1 (1,1) Q3 1 (1,1) Max 1 1 1 2.27 1 1.00 2.20 1.06 Descriptive summary statistics of Human Macrophage Inﬂammatory Protein-1 alpha concentration fold change from baseline by treatment. Descriptive summary statistics of Human Monocyte chemoattractant protein-1 (Monocyte Chemotactic and Activating Factor) concentration Table 63: Table 61: treatment. Table 64: Table 65: fold change from baseline by treatment. Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Confidential/Proprietary Information -28- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined Combined Combined n40 Min40 0.4840 0.68 Q140 0.88 0.45 1.00 0.38 Median 1.02 0.91 (95% (0.94,1.16) CI) 1.11 0.82 (1.05,1.23) 1.01 (0.96,1.12) 1.00 (0.86,1.11) Q3 1.25n 1.5040 4.48 1.29 Min Max 40 0.41 3.02 1.1640 0.50 2.44 Q140 0.96 0.32 3.22 0.83 0.23 Median 1.10 0.80 (95% (1.06,1.28) CI) 1.07 0.88 (0.95,1.14) 1.00 (0.91,1.23) 1.08 (1.01,1.18) Q3 1.42n 1.2740 1.86 1.32 Min Max 40 0.23 2.00 1.3440 0.23 2.05 Q140 1 0.26 3.65 1 0.26 Median 1 (95% CI) 1 1 (1,1.15) 1 (1,1.00) 1 (1,1.00) Q3 1 (1,1.00)n40 Min Max 40 2.14 0.2240 1.40 0.22 Q140 3.63 1.00 0.99 0.17 6.87 1.00 1.00 0.22 Median 5.85 1 0.98 (95% (1,1.12) CI) 5.04 1 1.00 (1,1.07) 1 (1,1.00) 1 (1,1.13) Q3n34 1.32 Min Max 35 0.78 1.2935 0.78 5.06 1.06 Q135 0.91 0.66 3.24 1.50 0.92 0.77 7.24 Median 0.97 0.90 9.08 (95% (0.93,1.01) CI) 0.98 0.92 (0.94,1.02) 0.96 (0.93,0.99) 0.96 (0.95,1.00) Q3 1.03 1.04 1.11 1.01 Max 1.14 1.01 1.29 1.13 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n18 Min18 0.5818 0.68 Q118 0.90 0.45 0.91 0.39 Median 1.03 0.84 (95% (0.91,1.12) CI) 1.03 0.76 (0.94,1.29) 0.99 (0.86,1.18) 0.90 (0.78,1.01) Q3 1.12n 1.4318 4.48 1.25 Min Max 18 0.63 2.38 1.0118 0.50 2.30 Q118 0.98 0.50 1.50 0.82 0.23 Median 1.14 0.83 (95% (1.00,1.34) CI) 1.08 0.96 (0.86,1.22) 1.12 (0.87,1.39) 1.07 (0.96,1.24) Q3 1.36n 1.2518 1.73 1.40 Min Max 18 0.23 2.00 1.2918 0.23 2.05 Q118 1 0.26 2.25 1 0.26 Median 1 (95% CI) 1 1 (1,1.75) 1 (1,1.00) 1 (1,1.00) Q3 1 (1,1.00)n18 Min Max 18 2.12 0.4818 1.00 0.27 Q118 3.44 1.00 0.96 0.17 6.87 1.00 1.00 0.39 Median 5.85 1 1.00 (95% (0.97,1.21) CI) 5.04 1 0.90 (1.00,1.08) 1 (1.00,1.03) 1 (0.94,1.00) Q3n 1.2115 1.11 Min Max 16 0.78 5.06 1.0416 0.78 3.13 1.00 Q116 0.88 0.73 4.86 0.89 0.77 3.96 Median 0.93 0.87 (95% (0.88,1.04) CI) 0.98 0.91 (0.89,1.04) 0.96 (0.88,1.04) 0.97 (0.91,0.99) Q3 1.03 1.04 1.11 1.04 Max 1.14 0.99 1.29 1.03 DVC-LVS DVC-LVS DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of Human RANTES concentration fold change from baseline by treatment. Descriptive summary statistics of Human Tumor necrosis factor - alpha concentration fold change from baseline by treatment. Table 67: Descriptive summary statistics of Human Vascular endothelial growth factor concentration fold change from baseline by treatment. n22 Min22 0.4822 0.89 Q122 0.83 0.78 1.08 0.38 Median 1.02 0.95 (95% (0.89,1.24) CI) 1.14 0.87 (1.10,1.29) 1.11 (0.97,1.18) 1.10 (0.93,1.19) Q3 1.26n 1.4822 2.03 1.26 Min Max 22 0.41 3.02 1.2322 0.68 2.44 Q122 0.97 0.32 3.22 0.87 0.42 Median 1.09 0.82 (95% (1.01,1.37) CI) 1.06 0.87 (0.92,1.24) 0.94 (0.84,1.21) 1.10 (0.94,1.27) Q3 1.49n 1.2622 1.86 1.24 Min Max 22 0.46 2.00 1.4422 0.42 1.92 Q122 1.00 0.36 3.65 1.00 0.31 Median 1 0.97 (95% (1,1.98) CI) 1 1.00 (1,1.58) 1 (1,1.00) 1 (1,1.00) Q3n22 2.07 Min Max 22 0.22 1.9622 0.22 3.63 1.00 Q122 1.00 0.22 2.54 1.23 1.00 0.22 4.15 Median 1.00 0.92 2.90 (95% (1,1.24) CI) 1.00 1.00 (1,1.31) 1.00 (1,1.00) 1.02 (1,1.44) Q3n 1.3419 1.38 Min Max 19 0.90 3.48 1.1719 0.88 3.24 1.55 Q119 0.94 0.66 7.24 0.94 0.88 9.08 Median 0.98 0.92 (95% (0.94,1.01) CI) 1.00 0.94 (0.94,1.03) 0.96 (0.92,0.99) 0.96 (0.94,1.03) Q3 1.02 1.03 1.10 0.99 Max 1.12 1.04 1.10 1.13 Descriptive summary statistics of natural killer cells (CD56 dim CD16- CCR5-) mean fluorescence intensity fold change from baseline by Descriptive summary statistics of Human Macrophage Inflammatory Protein-1 beta concentration fold change from baseline by treatment. Table 68: Table 69: Table 66: treatment. Table 70: Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14

Confidential/Proprietary Information -29- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Combined Combined Combined FC t-Statistic P FDR 2 Log 0.70 4.340.60 0.0001 0.0367 4.13 0.0002 0.048 n34 Min35 0.7935 0.78 Q135 0.87 0.73 0.87 0.77 Median 0.93 0.84 (95% (0.91,1.00) CI) 0.97 0.92 (0.88,0.98) 0.95 (0.90,0.98) 0.97 (0.94,1.01) Q3 1.01n 1.0034 1.20 1.01 Min Max 35 0.68 1.12 1.0135 0.61 1.14 Q135 0.82 0.41 1.15 0.86 0.61 Median 0.91 0.84 (95% (0.87,0.95) CI) 0.93 0.78 (0.88,1.00) 0.92 (0.88,0.96) 0.94 (0.84,1.00) Q3 0.98n 1.0534 10.82 1.01 Min Max 35 0.26 12.05 1.0735 0.26 18.10 Q135 0.75 0.14 18.42 0.83 0.26 Median 0.90 0.82 (95% (0.85,0.94) CI) 0.89 0.70 (0.84,0.98) 0.87 (0.84,0.94) 0.93 (0.81,1.03) Q3 0.98 1.03 1.66 1.03 Max 5.10 1.05 10.10 3.19 USAMARIID-LVS USAMARIID-LVS USAMARIID-LVS n15 Min16 0.7916 0.78 Q116 0.87 0.73 0.84 0.83 Median 0.92 0.83 (95% (0.87,1.03) CI) 0.94 0.91 (0.84,0.99) 0.92 (0.83,1.07) 0.95 (0.90,1.00) Q3 1.02n 0.9915 1.07 1.08 Min Max 16 0.68 1.12 1.0116 0.67 1.14 Q116 0.81 0.41 1.12 0.85 0.66 Median 0.87 0.76 (95% (0.81,0.99) CI) 0.92 0.81 (0.85,1.01) 0.92 (0.79,0.98) 0.95 (0.82,1.04) Q3 0.99n 1.0115 1.46 1.00 Min Max 16 0.26 1.59 1.0616 0.26 1.86 Q116 0.71 0.14 1.51 0.80 0.26 Median 0.85 0.71 (95% (0.70,0.98) CI) 0.89 0.75 (0.79,1.00) 0.87 (0.68,1.01) 0.90 (0.78,1.05) Q3 0.94 1.01 1.66 1.00 Max 1.88 1.06 2.68 1.70 Fc fragment of IgG, highceptor affinity (CD64), pseudogene Ib, receptor (CD64),Fc fragment of IgG, high affinity Ic, re- DVC-LVS DVC-LVS DVC-LVS Descriptive summary statistics of T-cells (CD69-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of B-cells (CCR5-) mean fluorescence intensity fold change from baseline by treatment. Descriptive summary statistics of T-cells (CD4+ CD69-) mean fluorescence intensity fold change from baseline by treatment. FCGR1C n19 Min19 0.8119 0.81 Q119 0.88 0.78 0.89 0.77 Median 0.96 0.88 (95% (0.91,1.00) CI) 0.97 0.95 (0.89,1.00) 0.96 (0.91,0.98) 0.98 (0.96,1.07) Q3 1.00n 1.0019 1.20 0.99 Min Max 19 0.76 1.03 1.0719 0.61 1.11 Q119 0.88 0.75 1.15 0.88 0.61 Median 0.93 0.88 (95% (0.88,0.95) CI) 0.93 0.76 (0.88,1.10) 0.91 (0.88,0.98) 0.93 (0.78,1.00) Q3 0.96n 1.1419 10.82 1.01 Min Max 19 0.71 12.05 1.0619 0.56 18.10 Q119 0.87 0.72 18.42 0.84 0.57 Median 0.92 0.83 (95% (0.88,0.97) CI) 0.89 0.70 (0.85,1.00) 0.87 (0.84,0.94) 0.94 (0.71,1.03) Q3 0.99 1.03 1.49 1.01 Max 5.10 1.04 10.10 3.19 Table 72: Table 71: Table 73: Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Study Visit Day 1 Day 2 Day 7 Day 14 Probe Set ID206513_PM_at204972_PM_at1568592_PM_at AIM2 Gene Name214511_PM_x_at OAS2 TRIM69 Gene Description FCGR1B, 230036_PM_at202270_PM_at absent in melanoma 2 2’-5’-oligoadenylate tripartite210166_PM_at synthetase motif SAMD9L 2, containing 69/71kDa 69226982_PM_at GBP11553785_PM_at TLR5225842_PM_at sterile alpha ELL2 motif domain containing RASGEF1B 9-like1556499_PM_s_at guanylate207978_PM_s_at binding COL1A1 PHLDA1 protein 1, interferon-inducible RasGEF domain209959_PM_at toll-like family, receptor member 5 1B NR4A3210004_PM_at elongation factor, RNA polymerase II, 2220612_PM_at collagen, pleckstrin NR4A3 type homology-like I, domain, alpha family A, 1 member 1 OLR1 nuclear receptor subfamily 4, group A, member 3 nuclear receptor subfamily 4, group A, member 3 oxidized low density lipoprotein (lectin-like) receptor 1 0.61 Homo sapiens PRO0641 protein (PRO0641), mRNA. 4.80 0.64 0.67 0.59 <0.0001 0.72 0.0248 -0.85 4.31 4.14 4.43 5.02 -0.83 -4.28 -0.63 0.0001 -1.26 0.0002 <0.0001 0.0381 0.0475 -4.21 <0.0001 0.033 -1.10 0.0001 -1.27 -4.19 0.0248 -4.60 0.0413 0.0002 -4.69 -4.69 -0.64 0.0002 <0.0001 -0.65 0.0432 0.0261 0.0448 <0.0001 <0.0001 -4.72 0.0248 0.0248 -4.43 <0.0001 <0.0001 0.0248 0.033

Confidential/Proprietary Information -30- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log -0.67 -5.00-0.72 <0.0001-0.76 -5.01 0.0248 -1.32 -5.18 <0.0001 0.0248 -5.69 <0.0001-1.21 0.0248 <0.0001 -8.01 0.0093 <0.0001 <0.0001 Log 0.79 6.52 <0.0001 0.0004 NULL RP1-93H18.6 STAT1 signal transducer and activator of transcription 1, 91kDa 0.82 6.50 <0.0001 0.0004 Differentially expressed genes (Combined Study Groups, Day 0 vs. 1). Sorted by descending t-statistic. Probe set annotations were 229625_PM_at212845_PM_at205931_PM_s_at GBP5202269_PM_x_at SAMD4A CREB5206513_PM_at GBP1232375_PM_at guanylate sterile binding alpha AIM2 protein motif 5 domain containing cAMP 4A responsive element binding protein 5 guanylate binding protein 1, interferon-inducible absent in melanoma 2 Homo sapiens cDNA FLJ12169 fis, clone MAMMA1000643 0.64 1.08 0.85 0.81 6.29 5.97 6.37 0.84 5.93 <0.0001 <0.0001 <0.0001 0.0005 0.0009 6.46 0.0005 <0.0001 0.0009 <0.0001 0.88 0.0004 5.95 <0.0001 0.0009 Probe Set ID226099_PM_at205476_PM_at217999_PM_s_at ELL2 Gene Name219557_PM_s_at CCL20 PHLDA11557049_PM_at Gene Description NRIP3211434_PM_s_at BTBD19217997_PM_at elongation factor, pleckstrin RNA CCRL2 homology-like chemokine polymerase domain, (C-C II, family motif) 2205330_PM_at A, ligand member 20 1239876_PM_at nuclear receptor PHLDA1 interacting protein 3 BTB (POZ)207850_PM_at domain MN1 containing 19 chemokine (C-C228536_PM_at motif) receptor-like 2244868_PM_at pleckstrin CXCL3 homology-like domain, family A, member1552711_PM_a_at 1 PRMT10209270_PM_at CYB5D1 meningioma (disrupted in balanced translocation)224978_PM_s_at 1 chemokine (C-X-C motif)210118_PM_s_at protein ligand LAMB3 arginine 3 methyltransferase USP36 10 (putative) cytochrome209383_PM_at b5 domain IL1A containing 11565701_PM_at239451_PM_at DDIT3 laminin, beta 3 ubiquitin specific peptidase 36 -0.87 interleukin 1, alpha DNA-damage-inducible transcript 3 -4.76 -0.68Probe Set Homo ID sapiens mRNA; -1.14 <0.0001 cDNA DKFZp451B0818231578_PM_at (from clone DKFZp451B0818) 0.0248 -0.99 -4.72 -0.88235175_PM_at223220_PM_s_at -4.92 -0.73 GBP1 Gene Name -0.70 -0.65229543_PM_at GBP4 -4.74 <0.0001 -4.83 PARP9 0.0248 Gene <0.0001 Description -4.93 -4.91 -0.63AFFX- -4.85 OTTHUMG00000159342, 0.0248 <0.0001 <0.0001 -0.70 guanylateHUMISGF3A/M97935_MA_at binding protein 0.0248 1, 0.0248 interferon-inducible poly guanylate <0.0001 (ADP-ribose) binding polymerase protein <0.0001 -5.00 family, 4 member <0.0001 9 0.0248 0.0248 -5.96 0.0248 -0.84 -0.59 <0.0001 0.0248 <0.0001 -5.00 0.0057 -5.02 <0.0001 -0.59 <0.0001 0.0248 -0.82 0.0248 -5.40 -5.96 <0.0001 0.0197 <0.0001 0.0057 1.37 0.79 7.06 6.67 <0.0001 0.0002 <0.0001 0.82 0.0003 6.78 <0.0001 0.0002 Table 74: obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Confidential/Proprietary Information -31- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.94 5.81 <0.0001 0.0011 0.96 5.65 <0.0001 0.0014 0.63 5.24 <0.0001 0.0027 0.72 5.000.74 <0.0001 0.0041 4.96 <0.0001 0.0043 Fc fragment of IgG, highceptor affinity (CD64),Fc Ia, fragment of receptor IgG, (CD64),Fc high fragment affinity of Ic, receptor IgG, (CD64), high pseudogene affinity Ib, re- Fc fragment of IgG, highceptor affinity (CD64), pseudogene Ib, receptor (CD64),Fc fragment of IgG, high affinity Ic, re- cAMP responsive element binding protein 5,uncharacterized LOC401317 0.63 5.48 <0.0001 0.0019 FCGR1B, FCGR1C FCGR1C STAT1 signal transducer and activator of transcription 1, 91kDaLOC401317 0.76 5.63 <0.0001 0.0015 202270_PM_at238581_PM_at229228_PM_at GBP1 GBP5 CREB5, guanylate binding protein 1, interferon-inducible guanylate binding protein 5 1.02 5.59 <0.0001 0.0015 0.75 5.57 <0.0001 0.0016 Probe Set ID216950_PM_s_at FCGR1A, Gene Name204439_PM_at212099_PM_at Gene Description 231577_PM_s_at IFI44L235276_PM_at RHOB GBP1200986_PM_at214511_PM_x_at EPSTI1 interferon-induced protein 44-like SERPING1 FCGR1B, ras homologAFFX- family guanylate member binding B protein 1, interferon-inducibleHUMISGF3A/M97935_MB_at serpin epithelial peptidase stromal inhibitor, interaction clade 1 G (breast) (C1 inhibitor), member 1227609_PM_at229450_PM_at218986_PM_s_at EPSTI1230036_PM_at IFIT3 DDX601561738_PM_at1568592_PM_at SAMD9L epithelial stromal interaction 11570541_PM_s_at (breast) DEAD TRIM69227807_PM_at (Asp-Glu-Ala-Asp) interferon-induced GBP1P1 box protein polypeptide with 0.99 60 tetratricopeptide repeats239661_PM_at 3 sterile alpha motif domain containing 9-like226603_PM_at 1.09 PARP9 tripartite226022_PM_at guanylate 5.68 motif binding containing protein 69 1, interferon-inducible pseudogene200628_PM_s_at 1 SAMD9L Homo sapiens 0.63 5.71 cDNA: FLJ20968226757_PM_at fis, clone SASH1 ADSU00702. poly WARS (ADP-ribose) <0.0001 polymerase 0.60202687_PM_s_at family, member 9 0.0014 0.59236439_PM_at sterile 5.79 <0.0001 alpha IFIT2 motif TNFSF10 domain containing 9-like214059_PM_at 0.0013 SAM 5.69 and SH3 tryptophanyl-tRNA219806_PM_s_at domain synthetase containing 5.78 1 <0.0001217502_PM_at tumor IFI44 necrosis factor 0.0012 SMCO4 (ligand) superfamily, member211864_PM_s_at 10 <0.0001 interferon-induced protein with tetratricopeptide repeats <0.0001 0.0014 1563509_PM_at 2 IFIT2 0.86 MYOF 0.0012 202688_PM_at single-pass membrane 0.83 protein232000_PM_at interferon-induced with protein coiled-coil 44 domains 4 5.45209417_PM_s_at TNFSF10 0.59 0.84 myoferlin interferon-induced protein 5.25 with IFI35 tetratricopeptide repeats 2 0.79 0.79 <0.0001 tumor necrosis 5.40 factor 0.002 (ligand) superfamily, 5.47 member 10 <0.0001 Homo sapiens mRNA; 5.30 cDNA 0.0027 DKFZp313O229 5.32 (from 0.59 clone interferon-induced DKFZp313O229) protein <0.0001 35 <0.0001 0.0022 Homo sapiens 0.002 cDNA FLJ11508 <0.0001 fis, clone <0.0001 HEMBA1002162 5.24 0.0024 0.74 0.72 0.74 0.0023 0.90 <0.0001 5.03 5.30 5.02 5.23 0.59 0.0027 0.59 0.67 0.78 0.61 <0.0001 <0.0001 <0.0001 <0.0001 4.97 4.93 0.004 0.0024 0.004 0.0027 5.23 4.97 5.20 0.75 <0.0001 <0.0001 0.0043 <0.0001 0.0046 0.0027 <0.0001 <0.0001 0.64 4.82 0.61 0.0043 0.0029 4.77 <0.0001 4.97 0.006 <0.0001 <0.0001 0.0067 0.0043 0.59 4.72 <0.0001 0.0071

Confidential/Proprietary Information -32- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.87 4.59 <0.0001 0.0085 0.670.68 4.14 4.06 0.0002 0.0002 0.0193 0.0218 -0.79 -4.00-0.60 0.0003 0.0244 -4.13 0.0002 0.0196 NULL STAT1 signal transducer and activator of transcription 1, 91kDa 0.64 4.67 <0.0001 0.0076 RP11- 769O8.3 204972_PM_at219386_PM_s_at214329_PM_x_at OAS2 SLAMF8201798_PM_s_at TNFSF10 MYOF SLAM family member 2’-5’-oligoadenylate 8 synthetase tumor 2, necrosis 69/71kDa factor (ligand) superfamily, member 10 myoferlin 0.94 0.67 4.63 4.66 <0.0001 0.0079 <0.0001 0.69 0.0076 4.66 <0.0001 0.0076 Probe Set ID204533_PM_atAFFX- HUMISGF3A/M97935_5_at CXCL10 Gene Name Gene Description chemokine (C-X-C motif) ligand 10238439_PM_at235574_PM_at203153_PM_at ANKRD22204747_PM_at GBP4232383_PM_at IFIT1 ankyrin repeat domain217518_PM_at 22 IFIT3242598_PM_at TFEC guanylate1563088_PM_a_at binding MYOF protein 4239196_PM_at interferon-induced LOC284837 protein with tetratricopeptide repeats235643_PM_at 1 interferon-induced protein with tetratricopeptide repeats transcription uncharacterized202869_PM_at 3 factor LOC284837 ANKRD22 EC myoferlin 227626_PM_at SAMD9L205476_PM_at OAS1 ankyrin repeat domain233121_PM_at 22 PAQR81564150_PM_a_at sterile alpha CCL20 motif domain containing 9-like203395_PM_s_at C12orf79 2’-5’-oligoadenylate232406_PM_at synthetase 1, progestin 40/46kDa HES1 and adipoQ 1.08 receptor230233_PM_at family member VIII chemokine (C-C chromosome motif)223767_PM_at 12 ligand open 20 reading frame 79218856_PM_at 4.71216243_PM_s_at GPR84 hairy 0.74 and enhancer Homo of sapiens split222180_PM_at cDNA 1, FLJ12299 TNFRSF21 0.63 (Drosophila) fis, IL1RN clone MAMMA1001851 <0.0001 0.0071 4.43 OTTHUMG00000178354, tumor G necrosis Homo protein-coupled factor sapiens receptor receptor 4.26226397_PM_s_at cDNA superfamily, 84 member FLJ13731 21 fis, clone PLACE3000142227613_PM_at interleukin 1 receptor <0.0001 antagonist 1.041565701_PM_at 0.0119 0.0001223484_PM_at ZNF331 0.67 0.0157 202948_PM_at 4.58205479_PM_s_at C15orf48 0.68206648_PM_at 4.51 IL1R1 zinc finger 0.72 PLAU protein 331 <0.0001 0.61 Homo217996_PM_at sapiens cDNA: FLJ21028 0.63 fis, 0.0086 0.84 clone chromosome CAE07155 15 ZNF571 open 3.99 -0.82 reading frame <0.0001 48 3.74 PHLDA1 Homo sapiens 3.62 0.01 mRNA; 0.70 cDNA interleukin DKFZp451B0818 1 3.64 (from plasminogen receptor, 4.24 clone activator, type urokinase DKFZp451B0818) I -3.82 0.0003 -0.62 zinc finger protein 0.0006 571 -0.62 pleckstrin 0.0009 0.0249 homology-like 3.88 -0.60 domain, family 0.0008 A, 0.0401 -1.29 0.0001 member -0.63 1 0.0005 0.0492 -3.84 0.0478 0.0162 -3.85 0.0346 -4.10 0.0004 -3.72 -3.84 -0.62 0.0005 0.0313 0.0004 0.0002 0.0334 0.0007 0.0328 0.0005 -4.22 0.0205 0.0422 0.0333 -0.64 -0.63 -0.72 0.0002 -4.06 0.0169 -4.11 -4.13 0.0002 0.0002 0.0002 0.0218 -0.97 -1.10 0.0201 0.0196 -4.24 -4.36 -0.80 -0.59 0.0001 <0.0001 -0.64 -4.15 0.0162 0.0134 -4.31 -4.30 0.0002 -0.64 0.0001 0.0192 0.0146 0.0001 -4.34 0.0149 0.0001 0.0138

Confidential/Proprietary Information -33- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.82 -4.38 <0.0001 0.0132 -1.54 -4.85-0.74 <0.0001 0.0057 -5.00 <0.0001 0.0041 -0.66 -5.39 <0.0001 0.0022 -0.81 -5.82 <0.0001 0.0011 Probe Set ID212158_PM_at202435_PM_s_at204614_PM_at SDC2 Gene Name CYP1B1237718_PM_at217127_PM_at SERPINB2 Gene Description 1565776_PM_at EIF4E cytochrome P450, family syndecan 1,202437_PM_s_at 2 subfamily CTH B, serpin polypeptide peptidase 1 inhibitor, clade224978_PM_s_at B (ovalbumin), member CYP1B1 2210139_PM_s_at USP36 eukaryotic202436_PM_s_at translation initiation factor PMP22 4E211434_PM_s_at cystathionase cytochrome (cystathionine CYP1B1 P450, gamma-lyase) family 1,213638_PM_at subfamily B, polypeptide CCRL2 1 ubiquitin210118_PM_s_at specific peptidase Homo 36 sapiens mRNA; peripheral cDNA myelin209803_PM_s_at DKFZp667M067 protein (from PHACTR1 22 clone cytochrome IL1A DKFZp667M067) P450, family 1,209959_PM_at subfamily B, polypeptide PHLDA2 1 chemokine (C-C1555638_PM_a_at motif) receptor-like 2 phosphatase and actin239876_PM_at SAMSN1 regulator NR4A3 11556499_PM_s_at pleckstrin homology-like interleukin domain, 1, family alpha 1553785_PM_at A, COL1A1 member 2 -1.23 SAM -0.69231972_PM_at domain, SH3 domain -0.84 nuclear and receptor nuclear RASGEF1B subfamily localization1563621_PM_at 4, signals group 1 A, member 3223394_PM_at collagen, -4.42 type -4.40 I, alpha -4.61 RasGEF 1 domain204567_PM_s_at family, member 1B222900_PM_at SERTAD1 ABCG1 <0.0001 <0.0001 -0.81227099_PM_s_at <0.0001 0.0121 0.0126 0.0081 205330_PM_at NRIP3 C11orf96 SERTA domain containing -0.81217998_PM_at -0.70 1 -4.63 Homo ATP-binding cassette, sapiens -0.75 sub-family210004_PM_at cDNA: G FLJ21028 MN1 Homo (WHITE), fis, sapiens member clone mRNA; 1 CAE07155 cDNA217997_PM_at DKFZp667O0416 (from PHLDA1 chromosome -4.56 clone -4.57 11 DKFZp667O0416) <0.0001 open nuclear reading receptor frame244044_PM_at interacting 96 OLR1 -4.67 protein 3 0.008 201490_PM_s_at PHLDA1 <0.0001 -0.70 <0.0001228536_PM_at -0.78 pleckstrin meningioma homology-like domain, (disrupted 0.0089 PPIF 0.0088 <0.0001 family -0.61 in A, balanced member translocation)1557049_PM_at 1 1 0.0076 -0.72 oxidized226099_PM_at -4.97 low pleckstrin -0.62 PRMT10 density homology-like -4.85 domain, lipoprotein family (lectin-like) -0.73 A, receptor BTBD19 member 1 -4.65217999_PM_s_at 1 -0.99 -1.36 -4.74209324_PM_s_at ELL2 <0.0001 peptidylprolyl PHLDA1 -4.66 isomerase <0.0001 F231779_PM_at protein -5.06 arginine 0.0043 <0.0001 methyltransferase RGS16 10 0.0057 -4.75 (putative) BTB -4.97 (POZ)244868_PM_at domain 0.0076 <0.0001 containing 19 <0.0001204790_PM_at 0.0069 IRAK2 pleckstrin <0.0001 homology-like domain, 0.0076 family <0.0001 A, elongation <0.0001 member factor, 0.0038 -0.59 RNA 1 polymerase II, regulator 0.0069 -0.86 2 of 0.0043 G-protein -0.82 SMAD7 signaling 16 interleukin-1 -5.10 receptor-associated kinase 2 -5.05 -5.06 -0.71 SMAD family member 7 <0.0001 <0.0001 -0.86 <0.0001 0.0036 -5.01 -0.77 0.0039 -0.68 0.0038 -0.62 -1.48 -0.80 -1.19 -5.37 <0.0001 -5.32 -5.25 -5.10 0.0041 -5.37 -5.14 -5.39 <0.0001 <0.0001 0.0022 <0.0001 <0.0001 0.0023 -0.66 <0.0001 0.0027 <0.0001 0.0036 <0.0001 0.0022 -0.98 0.0033 0.0022 -5.43 -5.66 <0.0001 -0.82 -0.68 -0.71 0.0021 <0.0001 0.0014 -0.68 -5.49 -0.84 -5.41 -5.57 -5.73 <0.0001 -5.68 <0.0001 <0.0001 0.0019 0.0022 0.0016 <0.0001 <0.0001 0.0013 0.0014 -0.70 -5.84 <0.0001 0.0011

Confidential/Proprietary Information -34- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log -1.03-0.64 -6.88-1.28 -7.02 <0.0001 -7.47 0.0002 <0.0001 0.0002 <0.0001 0.0002 Log 0.74 5.870.63 <0.0001 0.0006 0.66 5.42 5.350.59 <0.0001 0.0012 0.78 <0.0001 5.22 0.0014 5.21 <0.0001 0.0018 <0.0001 0.0019 0.60 5.04 <0.0001 0.0022 cAMP responsive element binding protein 5,uncharacterized LOC401317 0.65 5.81 <0.0001 0.0006 LOC401317 Differentially expressed genes (Combined Study Groups, Day 0 vs. 2). Sorted by descending t-statistic. Probe set annotations were Probe Set ID207978_PM_s_at219557_PM_s_at NR4A3237204_PM_at Gene Name NRIP3226833_PM_at225842_PM_at Gene Description nuclear receptor1565868_PM_at subfamily CYB5D1 4, group A, member227029_PM_at nuclear 3 receptor PHLDA1 interacting protein 3 CD44209270_PM_at209383_PM_at cytochrome FAM177A1 b5 domain containing 1203411_PM_s_at pleckstrin LAMB3 homology-like domain, family ESTs, A, Moderately member similar239451_PM_at 1 to DDIT3 family OVCA1 with LMNA CD44 sequence molecule similarity (Indian 177, blood member group) A1 laminin, beta 3 DNA-damage-inducible transcript 3 lamin A/C Probe Set ID209773_PM_s_at227618_PM_at RRM2229228_PM_at Gene Name -1.72229510_PM_at CREB5, Gene Description 1557302_PM_at ribonucleotide -5.87 reductase M2 -1.02213626_PM_at MS4A14 ZNF585B -1.14229670_PM_at <0.0001227038_PM_at -6.05 CBR4 0.001 -0.65202589_PM_at membrane-spanning 4-domains, -5.94 -0.77 zinc subfamily A, finger member protein 14225509_PM_at 585B SGMS2 <0.0001 -6.39 -0.661562289_PM_at TYMS 0.0009 <0.0001 -0.67 -5.99 carbonyl202503_PM_s_at reductase SAP30L 4 0.0009 213653_PM_at <0.0001 -5.97 sphingomyelin synthase KIAA0101 2226603_PM_at 0.0005 -6.29 <0.0001 thymidylate -0.92 0.0009 synthetase228157_PM_at METTL3 SAP30-like <0.0001 KIAA0101 1554696_PM_s_at SAMD9L 0.0009 <0.00011563509_PM_at TYMS -6.95 ZNF207 0.0005 228455_PM_at methyltransferase like Homo 3 sapiens mRNA; cDNA1566557_PM_at sterile DKFZp434N0220 (from alpha clone motif DKFZp434N0220) <0.0001 domain containing 9-like209200_PM_at zinc 0.0002 finger protein thymidylate 207 BAIAP2-AS1 synthetase230036_PM_at 0.681555882_PM_at MEF2C BAIAP2 antisense RNA 1 SAMD9L (head to head) 5.73 SPIN3 Homo sapiens mRNA; 0.59 cDNA DKFZp313O229 1.01 (from clone myocyte DKFZp313O229) enhancer factor 2C sterile alpha motif <0.0001 domain containing 9-like 0.0007 spindlin 5.22 family, member 6.09 3 <0.0001 <0.0001 0.0019 0.62 0.0004 0.60 5.58 5.06 0.61 0.81 <0.0001 0.68 <0.0001 5.31 0.0009 0.0022 5.19 5.28 <0.0001 0.60 0.62 0.0015 <0.0001 <0.0001 0.0019 5.20 0.59 4.94 0.0016 0.63 0.68 <0.0001 5.07 <0.0001 5.13 4.84 0.0019 0.0028 0.66 <0.0001 <0.0001 <0.0001 0.0022 4.91 0.002 0.62 0.0034 <0.0001 4.81 0.0029 <0.0001 0.0036 Table 75: obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Confidential/Proprietary Information -35- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.670.61 4.72 4.68 <0.0001 0.0041 <0.0001 0.0044 0.630.81 4.44 4.420.67 <0.0001 0.0067 0.68 <0.0001 0.007 0.67 4.34 4.340.61 4.28 0.0001 0.0001 0.008 4.24 0.0001 0.008 0.0089 0.00010.63 0.0095 3.96 0.0003 0.0149 Probe Set ID232383_PM_at201890_PM_at206513_PM_at TFEC Gene Name240061_PM_at RRM2223155_PM_at AIM2 Gene Description 213830_PM_at transcription232000_PM_at factor HDHD2 EC ribonucleotide reductase227626_PM_at M2 YME1L1213238_PM_at absent in melanoma 2243709_PM_at PAQR8 haloacid dehalogenase-like hydrolase domain235625_PM_at containing YME1-like ATP10D 2 1 ATPase 239301_PM_at SLC38A9242598_PM_at VPS41 progestin and adipoQ receptor243824_PM_at family ATPase, class member V, VIII type Homo 10D solute sapiens224962_PM_at carrier cDNA FLJ11508 family 38, fis, member clone 9 HEMBA10021621555037_PM_a_at LOC100996870 vacuolar protein sorting uncharacterized210166_PM_at IDH1 41 LOC100996870 C9orf69 homolog (S. cerevisiae)230918_PM_at 241917_PM_at TLR51552386_PM_at chromosome 9 open reading227052_PM_at frame isocitrate 69 dehydrogenase 1 (NADP+), soluble GAPT219243_PM_at 0.61226423_PM_at toll-like receptor 5 222691_PM_at GIMAP4 4.701563088_PM_a_at PAQR8 GRB2-binding adaptor protein,224358_PM_s_at transmembrane LOC284837 SLC35B3 0.69240238_PM_at GTPase, IMAP <0.0001 family MS4A7 member 4 0.65 0.72 uncharacterized227426_PM_at LOC284837 0.0042 progestin and 0.79 adipoQ solute receptor221895_PM_at carrier family family 4.68 member 35, VIII member B3218230_PM_at SOS1 4.77 4.59 membrane-spanning 0.60 4-domains,205898_PM_at subfamily 0.67 MOSPD2 A, 4.80 member 7 <0.0001202869_PM_at ARFIP1 0.0044 205552_PM_s_at <0.0001 <0.0001 CX3CR1 4.49 4.76 0.60 motile 0.0037 son 0.0053 <0.0001209995_PM_s_at sperm of OAS1 domain sevenless homolog containing OAS1 1 2 (Drosophila) 0.0036 39318_PM_at 0.62 ADP-ribosylation TCL1A factor 0.77 interacting protein <0.0001228190_PM_at chemokine 1 (C-X3-C <0.0001 4.49 motif) 0.59 receptor 1 0.0063 214329_PM_x_at 0.0038 TCL1A 4.56 2’-5’-oligoadenylate231956_PM_at 0.60 synthetase 2’-5’-oligoadenylate ATG4C 4.42 1, synthetase 40/46kDa TNFSF10 1, 40/46kDa T-cell <0.0001 leukemia/lymphoma224989_PM_at 4.37 1A 0.0062 <0.0001 RNF213 0.63 4.42 <0.0001 T-cell 0.0055 leukemia/lymphoma tumor 1A necrosis autophagy factor (ligand) related 0.007 <0.0001 superfamily, 4C, member cysteine 10 peptidase 0.0077 4.26 0.71 ring <0.0001 0.62 finger protein 213 0.0071 0.0001 4.18 4.07 0.61 Homo 0.0092 sapiens cDNA FLJ13289 0.65 fis, clone OVARC1001170 0.70 0.0002 0.0002 4.19 0.0103 0.0123 4.15 4.12 0.63 0.67 0.0002 0.0002 0.61 0.01 0.0002 3.94 0.61 0.0107 0.61 3.90 0.86 0.0114 0.72 3.92 0.0003 3.86 3.82 0.0004 3.87 3.73 0.0152 0.0164 0.0004 0.61 0.75 0.62 0.0004 0.0005 0.0159 0.0004 0.0006 0.0176 0.0189 0.017 3.74 0.68 0.0217 3.80 3.64 0.0006 3.78 0.0005 0.0008 0.0214 0.0194 0.0252 0.61 0.0006 0.0201 3.68 0.0007 0.0239

Confidential/Proprietary Information -36- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.74 -3.33 0.002 0.0427 -0.96-0.71 -3.66 -3.67 0.0008 0.0244 0.0008 0.0244 -0.74 -3.77 0.0006-0.87 0.0205 -3.97 0.0003 0.0147 TION WARNING ENTRY (H.sapiens) microRNA 155,MIR155 host gene (non-protein coding) -0.60 -4.01 0.0003 0.0137 MIR155HG Probe Set ID206978_PM_at216050_PM_at206641_PM_at CCR2 Gene Name205220_PM_at211924_PM_s_at TNFRSF17 Gene Description 218880_PM_at HCAR3 PLAUR chemokine204103_PM_at (C-C motif) tumor receptor necrosis 2 factor receptor211302_PM_s_at superfamily, member FOSL2 17202638_PM_s_at CCL4 hydroxycarboxylic PDE4B acid Homo receptor plasminogen sapiens 3 activator,1555167_PM_s_at cDNA: urokinase FLJ20931 receptor fis, ICAM1 clone ADSE01282225612_PM_s_at NAMPT FOS-like antigen 2 202637_PM_s_at B3GNT5 phosphodiesterase chemokine 4B,244840_PM_x_at cAMP-specific (C-C motif) ligand ICAM1 4 intercellular233899_PM_x_at adhesion nicotinamide molecule phosphoribosyltransferase 1 DOCK4213146_PM_at UDP-GlcNAc:betaGal ZBTB10 beta-1,3-N-acetylglucosaminyltransferase 51569477_PM_at intercellular203504_PM_s_at adhesion KDM6B molecule 1 dedicator of37028_PM_at cytokinesis 4 ABCA1 zinc finger and240859_PM_at BTB domain containing 10201325_PM_s_at lysine 0.62 (K)-specific PPP1R15A demethylase 6B235592_PM_at ZFYVE16 EMP1 ATP-binding cassette,1565776_PM_at sub-family A (ABC1), member protein 0.68 1 phosphatase 3.41237496_PM_at 1, regulatory Homo subunit sapiens, 15A clone zinc IMAGE:4291396, finger, mRNA FYVE domain containing -0.70 16226034_PM_at epithelial 3.56 membrane protein 0.0016 1 0.74206025_PM_s_at -0.62 0.0374 -3.42202948_PM_at DUSP4 TNFAIP6 0.001230380_PM_at -0.62 3.63 -3.30225955_PM_at IL1R1 0.0015 Homo sapiens 0.029 mRNA; cDNA206157_PM_at DKFZp667M067 -0.70 (from THAP2 tumor clone necrosis dual 0.0369 -3.24 DKFZp667M067) factor, specificity ESTs, alpha-induced 0.0022 phosphatase -0.63 protein Weakly 41564093_PM_at 0.0009 6 similar METRNL to ALU7_HUMAN1554786_PM_at 0.0452 ALU PTX3 0.0256 SUBFAMILY -3.36 SQ -0.70 SEQUENCE NEK1 interleukin -0.65 0.0025 CONTAMINA- 201631_PM_s_at 1 -3.41 receptor, type THAP I domain CASS4 containing, meteorin,240103_PM_at apoptosis 0.05 glial associated cell protein differentiation IER3 2 regulator-like 0.0018 -0.74 -3.35243659_PM_at -3.38 -0.63 0.0016 -0.66 pentraxin 0.0411 1558691_PM_a_at 3, LOC100996457 long -0.80 NIMA-related kinase 0.0373 1 uncharacterized242727_PM_at DOCK4 Cas LOC100996457 scaffolding -3.63 0.0019 protein 0.0017 family -3.44 member 4229437_PM_at -0.61 -3.44 immediate -0.65 0.0413 early -3.66 0.0395 -0.76 -0.61 response 3 ARL5B 0.0009 0.0014 MIR155, dedicator of -3.64 0.0015 cytokinesis 4 -3.59 0.0256 0.0008 -0.59 -3.44 -3.46 0.0355 0.036 0.0244 ADP-ribosylation factor-like 0.0008 5B 0.001 -3.64 0.0015 0.0014 0.0253 0.0356 0.0345 0.0271 -0.64 -0.80 0.0008 -0.59 0.0252 -3.65 -3.68 -3.70 -0.61 0.0008 -0.77 0.0007 0.0007 0.0249 -3.75 0.0237 0.0232 -3.67 -0.61 0.0006 -0.70 0.0008 0.021 -1.02 -3.70 0.0242 -3.94 -3.96 0.0007 -0.70 -0.64 0.0003 0.0232 0.0152 0.0003 -3.82 -3.95 -0.78 0.0148 -0.68 0.0005 0.0003 -3.99 0.0188 -4.01 0.0149 0.0003 0.0003 0.0143 0.0137

Confidential/Proprietary Information -37- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.65 -4.12 0.0002 0.0115 -0.61 -4.23 0.0001-0.95 0.0096 -4.29-0.71-0.67 0.0001-0.98 -4.34 0.0088 -4.34 -4.36 0.0001 0.0001 0.008 0.0001 0.008 0.0078 -0.66 -4.50 <0.0001 0.0062 -1.48 -4.68 <0.0001 0.0044 NULL RP6-99M1.2 Probe Set ID207850_PM_at219312_PM_s_at1564150_PM_a_at CXCL3 Gene Name ZBTB10202014_PM_at C12orf79230127_PM_at Gene Description PPP1R15A chemokine zinc (C-X-C finger chromosome motif) and205027_PM_s_at 12 ligand BTB open OTTHUMG00000184015, 3 domain reading containing frame 10 79224836_PM_at protein phosphatase MAP3K8 1, regulatory210954_PM_s_at subunit 15A230511_PM_at TP53INP2 TSC22D2209967_PM_s_at mitogen-activated protein kinase kinase1554980_PM_a_at kinase CREM 8 CREM tumor protein p53240207_PM_at TSC22 ATF3 inducible domain nuclear family, protein member 2 2220612_PM_at203505_PM_at cAMP responsive205193_PM_at cAMP element responsive modulator element modulator activating202933_PM_s_at transcription ABCA1 factor 3203888_PM_at MAFF YES1208868_PM_s_at204014_PM_at THBD ATP-binding GABARAPL1 cassette, sub-family A215889_PM_at (ABC1), member 1 Homo sapiens v-maf237252_PM_at PRO0641 GABA(A) musculoaponeurotic protein receptor-associated fibrosarcoma DUSP4 v-yes-1 (PRO0641), protein oncogene Yamaguchi sarcoma mRNA. like homolog viral 1 F oncogene (avian)203887_PM_s_at homolog SKIL 1 -0.72 -0.75 thrombomodulin 201324_PM_at -0.68 THBD THBD202437_PM_s_at dual -1.08 specificity -4.07 phosphatase 4204363_PM_at -0.62 -4.10 EMP1 CYP1B1 -4.09225539_PM_at SKI-like oncogene thrombomodulin -4.02219228_PM_at 0.0002 thrombomodulin F3 -4.17 0.0002 -0.80 0.000236711_PM_at ZBTB21 0.0123 cytochrome P450, 0.0118 family epithelial 1,208869_PM_s_at membrane subfamily 0.0122 protein ZNF331 0.0003 B, 1 polypeptide 1 -0.96 0.0002206983_PM_at -4.18 0.0135 GABARAPL1 MAFF 0.0104 209099_PM_x_at -0.61 zinc finger and BTB coagulation domain216066_PM_at -4.26 GABA(A) factor containing receptor-associated CCR6 III zinc 21 0.0002 protein (thromboplastin, finger -0.99 JAG1 like tissue protein -0.68 1 factor) -0.91 331203394_PM_s_at -4.19 0.0102 211840_PM_s_at -0.66 ABCA1 v-maf -0.60 0.0001 musculoaponeurotic HES1 fibrosarcoma oncogene -4.19 homolog225754_PM_at -4.24 F -4.20 (avian) PDE4D -0.70 0.0093 chemokine 0.0002240024_PM_at (C-C motif) jagged receptor -4.23 1 6 -4.28202988_PM_s_at 0.0101 -0.64 0.0002 AP1G1 0.0001 ATP-binding 0.0002 cassette, sub-family -4.22 A210118_PM_s_at (ABC1), SEC14L2 hairy member 0.0101 and 1 RGS1 0.0095 enhancer 0.01 phosphodiesterase 0.0001 of 4D, split 0.0001 cAMP-specific 1, (Drosophila) IL1A -4.31 0.0096 0.0089 0.0002 adaptor-related protein SEC14-like complex 2 1, (S. gamma cerevisiae) 1 0.0097 subunit -0.86 0.0001 regulator of G-protein signaling 1 -0.98 0.0085 interleukin 1, alpha -0.64 -4.40 -4.48 -0.65 -4.32 <0.0001 0.0073 <0.0001 -0.66 -0.64 -4.41 0.0063 -0.85 0.0001 0.0083 -4.47 -4.49 -0.60 <0.0001 -4.40 0.0071 <0.0001 <0.0001 -4.51 <0.0001 0.0064 0.0063 0.0073 -1.03 -0.66 -0.59 -0.72 <0.0001 -0.64 0.0061 -4.47 -4.58 -4.49 -4.51 -4.53 <0.0001 <0.0001 <0.0001 <0.0001 0.0064 0.0054 0.0062 0.0061 <0.0001 -0.62 -0.83 0.0059 -4.59 -4.64 <0.0001 <0.0001 0.0053 0.0048

Confidential/Proprietary Information -38- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.70 -4.74-0.62 <0.0001-0.96 0.0039 -0.74 -4.78 -4.78 -4.79 <0.0001 0.0037 <0.0001 0.0037 <0.0001-0.59 0.0036 -4.84 <0.0001 0.0034 -0.90 -5.05-0.66 <0.0001 -5.12 0.0022 -0.97 <0.0001 0.002 -5.13-0.66 <0.0001 -5.16 0.002 <0.0001 0.002 NULL RP11- 425D10.10 Probe Set ID202932_PM_at202684_PM_s_at205476_PM_at YES1 Gene Name RNMT202435_PM_s_at243771_PM_at CCL20 Gene Description CYP1B1222670_PM_s_at v-yes-1233952_PM_s_at RNA Yamaguchi sarcoma (guanine-7-) viral methyltransferase MAFB oncogene homolog 1214508_PM_x_at cytochrome ZBTB21 chemokine P450, (C-C family 1, motif)1554929_PM_at subfamily ligand B, 20 polypeptide CREM 1239827_PM_at SIK3227140_PM_at v-maf musculoaponeurotic fibrosarcoma zinc oncogene finger homolog and202436_PM_s_at B BTB (avian) RGCC domain containing 21204567_PM_s_at cAMP responsive INHBA element CYP1B1 modulator212659_PM_s_at ABCG1 SIK207630_PM_s_at family kinase 3 IL1RN regulator of210793_PM_s_at cell cycle cytochrome CREM P450, inhibin, family beta 1, A 230218_PM_at subfamily B, polypeptide NUP98 1 ATP-binding cassette, sub-family217996_PM_at G (WHITE), member 1218856_PM_at interleukin HIC1 1 receptor antagonist -0.68 -0.73218631_PM_at cAMP responsive PHLDA1 element modulator nucleoporin206374_PM_at 98kDa TNFRSF21 -0.761554095_PM_at AVPI1 -4.76 -4.71227093_PM_at pleckstrin hypermethylated DUSP8 homology-like in tumor domain, cancer necrosis family 1 factor A, receptor RBM33 member1557166_PM_at superfamily, member 1 -4.73 21 <0.0001 <0.0001 -0.62227099_PM_s_at USP36 0.0038 0.0042 arginine PDCD4 vasopressin-induced244054_PM_at 1 dual C11orf96 <0.0001 specificity phosphatase 8209325_PM_s_at RNA -4.72 binding 0.004 motif protein 33 -1.641554906_PM_a_at -0.67 RGS16 ubiquitin specific peptidase1556676_PM_a_at programmed 36 MPHOSPH6 cell chromosome death 11 <0.0001 4 open (neoplastic reading -0.79 transformation frame OTTHUMG00000175937, inhibitor) 96 -4.72 0.0041 -0.72 -0.92 -4.77 M-phase phosphoprotein 6 regulator of205479_PM_s_at G-protein -4.80 signaling 16 <0.0001 -4.80212158_PM_at -4.78 <0.0001 0.0041 PLAU 0.0038 210837_PM_s_at <0.00011570432_PM_at <0.0001 SDC2 0.0036 <0.0001 PDE4D 0.0036 243605_PM_at 0.0037 -0.76 -1.441552711_PM_a_at plasminogen activator, urokinase -1.06204491_PM_at CYB5D1 -0.78 phosphodiesterase -4.92 syndecan 4D,230652_PM_at cAMP-specific 2 -4.90 -4.81 PDE4D -0.82 -4.80 cytochrome <0.0001 b5 ARAF domain <0.0001 containing 1 0.0029 Homo 0.0031 sapiens <0.0001 clone -5.03 pp10199 <0.0001 unknown mRNA. 0.0035 -0.70 phosphodiesterase 4D, cAMP-specific 0.0036 v-raf -0.62 murine <0.0001 sarcoma 3611 viral -4.85 oncogene 0.0023 homolog -0.69 -0.74 -4.93 -0.65 <0.0001 -0.67 -4.96 0.0034 -5.05 <0.0001 -4.97 -0.60 0.0028 -5.01 <0.0001 <0.0001 -0.71 0.0026 <0.0001 0.0022 -5.06 0.0026 <0.0001 -5.10 0.0024 <0.0001 -0.72 -0.86 <0.0001 0.0022 0.0021 -0.77 -5.12 -5.15 -0.76 -0.63 -5.16 -0.74 <0.0001 <0.0001 -5.17 0.002 0.002 -5.16 <0.0001 0.002 -5.16 <0.0001 <0.0001 0.0019 0.002 <0.0001 0.002

Confidential/Proprietary Information -39- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.84 -5.20-0.60 <0.0001 -5.29 0.0019 <0.0001 0.0016 -0.62 -5.47-0.72 <0.0001-1.24 0.0011 -5.54 -5.56 <0.0001 0.0009 <0.0001 0.0009 -0.70 -5.61 <0.0001-0.66 0.0009 -5.68 <0.0001 0.0008 SFT2 domain containing 3,WD repeat domain 33 -0.73 -5.59 <0.0001 0.0009 WDR33 Probe Set ID231972_PM_at204015_PM_s_at201195_PM_s_at Gene Name DUSP4244868_PM_at SLC7A5215485_PM_s_at Gene Description 226833_PM_at ICAM1 dual specificity1554600_PM_s_at phosphatase 4 solute carrier family1555638_PM_a_at 7 LMNA CYB5D1 (amino acid transporter Homo light sapiens chain,201489_PM_at cDNA: SAMSN1 L FLJ21028 system), fis, member clone 5 CAE07155 intercellular239835_PM_at adhesion molecule 1227613_PM_at cytochrome PPIF b5 domain containing lamin 1 SAM A/C 241985_PM_at domain, SH3 KBTBD8 domain and nuclear localization221563_PM_at signals ZNF331 1227333_PM_at JMY -0.96223767_PM_at kelch peptidylprolyl DUSP10 repeat isomerase and F BTB (POZ) domain204087_PM_s_at containing zinc 8 finger protein 331226922_PM_at -5.20 GPR84 SLC5A6223028_PM_s_at dual specificity junction phosphatase mediating 10 and regulatory219199_PM_at protein, RANBP2 p53 cofactor <0.0001 SNX91556499_PM_s_at 0.0019 G solute protein-coupled carrier receptor family217127_PM_at 84 5 COL1A1 AFF4 (sodium-dependent vitamin transporter), Homo member sapiens 6239567_PM_at RAN cDNA: -0.81 binding FLJ23546 protein fis, clone 2 LNG08361230233_PM_at CTH sorting nexin 9 -0.88217997_PM_at collagen, type I, -5.20 alpha 1210836_PM_x_at AF4/FMR2 family, member 4204614_PM_at -5.33 PHLDA1 -0.81 PDE4D <0.0001228536_PM_at cystathionase (cystathionine gamma-lyase) 0.0019 218851_PM_s_at SERPINB2 <0.0001 -0.62 -5.20 -0.70 pleckstrin PRMT10 0.0015 homology-like -0.77 domain, SFT2D3, family phosphodiesterase A, 4D, member -0.77211423_PM_s_at cAMP-specific 1 serpin peptidase inhibitor, clade -5.45202068_PM_s_at B <0.0001 -5.21 (ovalbumin), member SC5D -0.90 2 -5.26244578_PM_at protein 0.0019 arginine -5.38 methyltransferase LDLR 10 (putative)206648_PM_at <0.0001 <0.0001 -5.41223887_PM_at <0.0001 0.0011 LCP2 0.0019 <0.0001 0.0017 204435_PM_at -0.59 sterol-C5-desaturase ZNF571 0.0013 -0.71222900_PM_at GPR132 <0.0001 low density lipoprotein receptor233121_PM_at 0.0012 NUPL1 -0.61 -5.42 lymphocyte211434_PM_s_at cytosolic NRIP3 -5.36 zinc -1.24 protein finger 2 protein (SH2 571 domain226397_PM_s_at containing G leukocyte protein-coupled protein receptor CCRL2 of 132 76kDa) -5.42 <0.0001 -0.90 nucleoporin <0.0001 -5.40 like 0.0012 1 0.0013 nuclear receptor interacting <0.0001 protein 3 -5.44 -1.44 chemokine -1.72 (C-C -0.77 0.0012 <0.0001 motif) receptor-like 2 -0.68 0.0012 -0.60 Homo sapiens <0.0001 cDNA -5.57 -0.63 -5.58 FLJ12299 fis, -5.54 clone MAMMA1001851 -0.89 0.0012 Homo -5.66 sapiens cDNA: -5.45 FLJ21028 fis, clone -0.76 -0.76 CAE07155 <0.0001 -5.49 <0.0001 <0.0001 -5.54 0.0009 <0.0001 0.0009 0.0009 <0.0001 0.0008 -5.59 -5.57 0.0011 <0.0001 <0.0001 0.0011 0.0009 <0.0001 <0.0001 0.0009 0.0009 -0.69 -1.03 -5.62 -0.75 -5.69 -1.05 -0.81 -0.96 <0.0001 -1.01 -5.68 <0.0001 0.0009 -5.78 0.0008 -5.68 -5.67 -5.69 <0.0001 0.0008 <0.0001 <0.0001 0.0007 <0.0001 0.0008 <0.0001 0.0008 0.0008

Confidential/Proprietary Information -40- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -1.01-0.67 -5.94 -5.99 <0.0001 0.0005 <0.0001 0.0005 -0.59-0.68 -6.11 -6.15 <0.0001 0.0004 <0.0001-0.59 0.0004 -6.29 <0.0001 0.0003 -1.15 -6.51 <0.0001 0.0003 adenosine A2a receptor,SPECC1L-ADORA2A readthrough -0.75 -6.53 <0.0001 0.0003 SPECC1L- ADORA2A Probe Set ID203395_PM_s_at226982_PM_at HES1217999_PM_s_at Gene Name212722_PM_s_at ELL2 PHLDA1206173_PM_x_at Gene Description JMJD6224978_PM_s_at hairy and GABPB1 enhancer of split213638_PM_at 1, (Drosophila) pleckstrin USP36 homology-like domain, family239876_PM_at A, elongation member factor, RNA 1 polymerase II, jumonji 2238756_PM_at domain PHACTR1 containing GA 6 binding protein transcription223915_PM_at factor, beta subunit 1 ubiquitin217998_PM_at specific GAS2L3 peptidase 36 phosphatase and actin225842_PM_at regulator BCOR 1237204_PM_at PHLDA11565868_PM_at growth PHLDA1 arrest-specific 2 like 3207826_PM_s_at BCL6 CD44 corepressor 243829_PM_at pleckstrin homology-like domain, ID3 family A, member201490_PM_s_at pleckstrin 1 homology-like domain, family A, member241970_PM_at 1 BRAF PPIF213452_PM_at CD44 molecule (Indian216350_PM_s_at blood group) ESTs, Moderately inhibitor similar201712_PM_s_at -1.06 of to ZNF184 DNA OVCA1 binding ZNF10 3, dominant v-raf228749_PM_at negative murine helix-loop-helix sarcoma protein viral peptidylprolyl RANBP2 oncogene isomerase homolog F B1237718_PM_at -0.69 -0.77 -5.87205330_PM_at ZDBF2 zinc finger protein 184 zinc203411_PM_s_at finger EIF4E protein RAN -5.91 -5.79 10 binding -0.88 protein <0.0001 2210004_PM_at MN1 LMNA 0.0006 220370_PM_s_at zinc finger, <0.0001 <0.0001 -5.81 DBF-type204790_PM_at containing OLR1 2 USP36 0.0005 0.0006 eukaryotic223484_PM_at translation initiation -0.69 factor 4E -1.02209803_PM_s_at lamin SMAD7 <0.0001 meningioma A/C -1.23 -0.66 (disrupted -0.78 in -1.18 balanced translocation)232406_PM_at 0.0006 1 C15orf48 PHLDA2 -5.87 ubiquitin oxidized209270_PM_at specific low -6.01 peptidase density 36 lipoprotein (lectin-like) -5.92 -6.07 receptor 1 -5.92205013_PM_s_at -6.02 SMAD family member 7 chromosome <0.0001 15 LAMB3 open -0.83 pleckstrin <0.0001 reading ADORA2A, homology-like frame domain, 0.0006 48 family <0.0001 A, <0.0001 member 0.0004 <0.0001 2 <0.0001 0.0005 0.0004 1557049_PM_at 0.0005 0.0004 -0.61 -5.97231779_PM_at laminin, beta -0.76 BTBD19 3 209959_PM_at Homo sapiens -0.75 -6.08236402_PM_at cDNA <0.0001 FLJ13731 IRAK2 fis, clone PLACE3000142 0.0005 -6.05 NR4A3 BTB (POZ) domain BRAF -6.05 <0.0001 containing 19 0.0004 <0.0001 interleukin-1 receptor-associated kinase -0.82 0.0004 2 nuclear <0.0001 receptor subfamily 4, -1.04 group A, 0.0004 member 3 v-raf murine sarcoma -1.64 viral -6.08 oncogene homolog -1.21 B1 -0.73 -0.66 -6.24 -0.66 -6.31 <0.0001 -1.12 -6.22 -6.13 0.0004 -6.16 <0.0001 -6.16 0.0003 <0.0001 -6.44 <0.0001 -0.97 0.0003 <0.0001 <0.0001 -1.60 0.0003 -0.77 0.0004 0.0004 <0.0001 <0.0001 0.0004 -6.47 0.0003 -6.42 -6.36 -0.80 <0.0001 <0.0001 <0.0001 0.0003 0.0003 0.0003 -6.37 -2.10 -0.70 -0.71 <0.0001 -0.92 0.0003 -6.61 -6.55 -6.68 -6.54 <0.0001 <0.0001 0.0003 <0.0001 <0.0001 0.0003 0.0003 0.0003

Conﬁdential/Proprietary Information -41- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log -1.46 -8.61 <0.0001 <0.0001 Log 0.74 7.87 <0.0001 <0.0001 0.910.70 6.78 6.60 <0.0001 0.0001 0.83 <0.0001 0.0001 0.73 6.45 6.37 <0.0001 0.0002 <0.0001 0.0002 cAMP responsive element binding protein 5,uncharacterized LOC401317 0.83 7.63 <0.0001 <0.0001 LOC401317 Differentially expressed genes (Combined Study Groups, Day 0 vs. 7). Sorted by descending t-statistic. Probe set annotations were Probe Set ID219557_PM_s_at1553785_PM_at NRIP3223394_PM_at Gene Name RASGEF1B226099_PM_at209324_PM_s_at SERTAD1 Gene Description RasGEF domain227029_PM_at nuclear family, receptor ELL2 member interacting 1B RGS16 protein 3207978_PM_s_at SERTA domain containing209383_PM_at 1 FAM177A1 NR4A3239451_PM_at regulator of elongation G-protein DDIT3 factor, signaling family RNA with 16 polymerase sequence II, similarity 2 177, member A1 nuclear receptor subfamily 4, group A, member 3 DNA-damage-inducible transcript 3Probe Set ID235286_PM_at 229228_PM_at Gene Name242943_PM_at CREB5, 230036_PM_at Gene Description 223220_PM_s_at ST8SIA4210166_PM_at SAMD9L PARP9239108_PM_at -1.32 -1.37225509_PM_at ST8 alpha-N-acetyl-neuraminide TLR5 alpha-2,8-sialyltransferase 41566501_PM_at sterile alpha FAR2 motif -0.73 domain containing poly 9-like (ADP-ribose)232382_PM_s_at polymerase SAP30L -6.81 family, -6.68 member 9 -2.20226603_PM_at -0.97 PCMTD1 -0.80 -7.211552334_PM_at toll-like receptor 5 -0.97 <0.0001 <0.0001 fatty227618_PM_at acyl -7.27 SAMD9L SAP30-like CoA reductase 0.0002 0.0003 2 TRIOBP -6.98206513_PM_at -6.82 protein-L-isoaspartate <0.0001 (D-aspartate) O-methyltransferase domain -7.02 containing213830_PM_at 0.0001 1 <0.0001 -1.09217143_PM_s_at sterile alpha AIM2 <0.0001 Homo 0.0001 motif sapiens domain <0.0001 cDNA containing TRIO FLJ20787 9-like202687_PM_s_at and ﬁs, 0.0002 clone F-actin YME1L1 <0.0001 COL02178. binding 0.0002 TRDC, protein TRDC218943_PM_s_at 0.0002 -8.07 TNFSF10 0.69226853_PM_at T cell receptor DDX58 delta constant230261_PM_at absent YME1-like 1 in 0.59 ATPase melanoma <0.0001 2232829_PM_at tumor 7.29 BMP2K necrosis <0.0001 factor (ligand) superfamily, member230860_PM_at 10 ST8SIA4 DEAD225669_PM_at (Asp-Glu-Ala-Asp) 6.51 box OR52K3P polypeptide 58 <0.0001232383_PM_at CEP19 BMP2 inducible <0.0001 0.61 kinase ST8 alpha-N-acetyl-neuraminide IFNAR1 alpha-2,8-sialyltransferase 0.82 4 <0.0001 olfactory receptor, family 52, TFEC subfamily 0.0002 K, member 3 pseudogene 7.02 centrosomal protein 19kDa 7.23 interferon (alpha, beta and omega) receptor 1 0.78 <0.0001 transcription factor EC <0.0001 <0.0001 <0.0001 6.56 0.91 0.60 0.67 <0.0001 6.48 0.66 0.0002 0.61 0.64 6.76 6.32 <0.0001 6.23 0.0002 0.62 6.46 6.18 <0.0001 0.66 <0.0001 0.0001 0.0002 <0.0001 6.24 <0.0001 <0.0001 0.0002 6.34 0.0002 0.0002 0.83 <0.0001 0.69 0.0002 <0.0001 6.39 0.0002 0.62 6.11 <0.0001 0.64 0.0002 6.24 <0.0001 0.0003 6.17 <0.0001 1.03 0.0002 <0.0001 0.0002 6.08 <0.0001 0.0003 Table 76: obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Confidential/Proprietary Information -42- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.64 6.050.72 <0.0001 0.0003 0.75 5.93 5.90 <0.0001 0.0003 0.63 <0.0001 0.0003 5.820.63 <0.0001 0.0004 5.75 <0.0001 0.0005 0.72 5.56 <0.0001 0.0006 0.67 5.41 <0.0001 0.0007 mRNA, complete cds. Probe Set ID216191_PM_s_at222981_PM_s_at YME1L1202688_PM_at Gene Name RAB10230836_PM_at1554948_PM_at TNFSF10 Gene YME1-like Description 1 ATPase ST8SIA4 RAB10,240061_PM_at member RAS oncogene family tumor necrosis229510_PM_at factor (ligand) superfamily, member 10236995_PM_x_at ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4203153_PM_at MS4A14 TFEC243736_PM_at 204007_PM_at IFIT1 Homo sapiens, Similar to hypothetical64883_PM_at protein membrane-spanning PRO2852, 4-domains, clone subfamily MGC:23787 A, IMAGE:4249212, member 14208304_PM_at FCGR3B transcription factor EC1562031_PM_at MOSPD2203128_PM_at interferon-induced CCR3 protein with tetratricopeptide repeats JAK2 Fc222793_PM_at 1 fragment of IgG, low affinity221895_PM_at IIIb, receptor SPTLC2 motile (CD16b) sperm domain containing 2210556_PM_at DDX58 0.70 chemokine224358_PM_s_at (C-C MOSPD2 motif) receptor 3 Janus kinase229450_PM_at 2 0.72 serine NFATC3 palmitoyltransferase, long MS4A7 chain base201193_PM_at subunit 5.94 2 DEAD (Asp-Glu-Ala-Asp) motile box229670_PM_at sperm polypeptide IFIT3 58 domain containing 2 5.97217104_PM_at nuclear 0.59 IDH1 factor of activated <0.0001 T-cells, membrane-spanning cytoplasmic, 4-domains,1568592_PM_at calcineurin-dependent subfamily 3 0.72 A, member 0.0003 7211138_PM_s_at ST20 <0.0001 5.99 TRIM69225290_PM_at 0.0003 interferon-induced protein with KMO tetratricopeptide repeats 5.90214329_PM_x_at 3 isocitrate 0.87 dehydrogenase 1 (NADP+), soluble225095_PM_at ETNK1 <0.0001 TNFSF10 tripartite243954_PM_at suppressor motif 0.0003 of containing <0.0001 tumorigenicity 69 20 5.87 0.79230098_PM_at SPTLC2 0.0003 kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)226022_PM_at tumor LINC00877 necrosis factor 0.67 ethanolamine (ligand) kinase superfamily, 1 member212632_PM_at 10 PHF20L1 <0.0001 5.82206207_PM_at serine SASH1 long 0.0004 palmitoyltransferase, long intergenic 0.59 chain non-protein base coding1552386_PM_at subunit RNA 5.64 2 STX7 877 PHD1563088_PM_a_at finger 0.64 <0.0001 CLC protein 20-like 1 GAPT 0.0004 227038_PM_at 0.62 LOC284837 5.73 0.72 SAM <0.0001 and SH3224009_PM_x_at domain 0.65 containing 1 0.0005 5.88 0.62 uncharacterized syntaxin226757_PM_at LOC284837 7 SGMS2 0.80 DHRS9 5.79 <0.0001 5.61 Charcot-Leyden GRB2-binding crystal 0.0005 adaptor galectin 5.70 protein, transmembrane IFIT2 <0.0001 5.79 0.75 5.57 0.0004 <0.0001 sphingomyelin <0.0001 synthase 2 dehydrogenase/reductase (SDR 0.61 family) 0.0004 member 0.0005 <0.0001 9 0.63 <0.0001 0.0005 5.67 <0.0001 0.0004 interferon-induced protein 0.0006 0.94 with 5.49 tetratricopeptide repeats 2 5.57 <0.0001 0.59 0.0005 5.45 <0.0001 <0.0001 0.0006 0.64 0.0006 5.45 0.63 0.62 <0.0001 0.0007 5.53 <0.0001 5.51 5.43 0.0007 0.62 <0.0001 0.76 0.0006 <0.0001 <0.0001 0.62 0.0006 0.0007 0.63 0.71 5.45 0.61 5.41 5.42 0.74 5.42 5.34 <0.0001 0.72 5.33 0.0007 <0.0001 0.0007 <0.0001 5.40 <0.0001 <0.0001 5.41 0.0007 <0.0001 0.0007 0.0008 0.75 0.0008 <0.0001 <0.0001 0.0007 0.0007 5.35 <0.0001 0.0008

Confidential/Proprietary Information -43- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.960.68 5.28 5.28 <0.0001 0.0009 <0.0001 0.0009 0.66 5.01 <0.0001 0.0014 0.640.72 4.94 4.930.76 <0.0001 0.0017 <0.0001 4.91 0.0017 0.59 <0.0001 4.90 0.0017 <0.0001 0.0018 heat shock 70kDa protein 1A,heat shock 70kDa protein 1BFc fragment of IgG,receptor low (CD16b) affinity IIIa, receptor (CD16a),Fc fragment of IgG, low affinity IIIb, 0.77 4.99 <0.0001 0.0015 HSPA1B FCGR3B Probe Set ID209200_PM_at242598_PM_at 222388_PM_s_at MEF2C Gene Name201798_PM_s_at VPS35218230_PM_at Gene Description MYOF219093_PM_at myocyte enhancer factor 2C223155_PM_at ARFIP1 vacuolar226423_PM_at protein PID1 sorting 35 homolog (S. cerevisiae)223583_PM_at myoferlin HDHD2209960_PM_at PAQR8 ADP-ribosylation factor interacting protein1566557_PM_at 1 TNFAIP8L2227626_PM_at phosphotyrosine HGF interaction haloacid domain dehalogenase-like containing hydrolase BAIAP2-AS1 domain 1218303_PM_x_at containing tumor 2 necrosis progestin factor, and alpha-induced adipoQ protein receptor235625_PM_at 8-like family PAQR8 2 member VIII BAIAP2 KRCC1 antisense RNA213238_PM_at 1 (head to head)232724_PM_at VPS41 hepatocyte growth factor (hepapoietin A;224962_PM_at scatter ATP10D factor) progestin and lysine-rich adipoQ coiled-coil receptor219243_PM_at 1 family MS4A6A member VIII213626_PM_at C9orf69 vacuolar protein sorting226047_PM_at 41 ATPase, GIMAP4 class homolog V, type (S. 10D cerevisiae)200799_PM_at membrane-spanning CBR4 4-domains, subfamily A, member 6A 0.60 MRVI1 chromosome 9 open reading1562289_PM_at frame GTPase, 69 HSPA1A, IMAP family member 4238992_PM_at 0.60 5.28 carbonyl227052_PM_at reductase 4 murine retrovirus integration230918_PM_at site POLI 1 0.81 homolog 0.66 5.25 0.60219607_PM_s_at 0.70 <0.0001 0.82202451_PM_at 0.0009 MS4A4A 5.27204006_PM_s_at 5.29 0.64 <0.0001 5.26 5.20 polymerase 0.0009 GTF2H1 Homo (DNA sapiens directed) 5.22 FCGR3A, mRNA; iota cDNA205552_PM_s_at DKFZp434N0220 (from membrane-spanning clone <0.0001 4-domains, DKFZp434N0220) subfamily 0.63 A, <0.0001 5.17 0.78 <0.0001244298_PM_at member 4A <0.0001 0.0009 OAS1 0.0009 0.0009 222691_PM_at <0.0001 0.60 general 0.001 transcription factor IIH, 0.69 polypeptide 0.001 1552553_PM_a_at 1, 62kDa 5.17 <0.0001 5.15229007_PM_at NLRC4 SLC35B3 0.001 5.07205898_PM_at 2’-5’-oligoadenylate synthetase 5.09 1, 40/46kDa 0.63 <0.0001225989_PM_at <0.0001 LOC283788 0.0011 solute 0.0011 1555037_PM_a_at carrier family CX3CR1 <0.0001 35, NLR member family, CARD B3 domain <0.0001207008_PM_at containing FSHD 0.0013 IDH1 HERC4 4 region 4.97 gene 0.61 1 0.0012 pseudogene 0.72 chemokine 0.76 CXCR2 (C-X3-C motif) receptor 1 0.66 <0.0001 5.10 HECT 0.69 and 5.05 RLD 0.0016 domain isocitrate containing dehydrogenase E3 1 0.63 ubiquitin (NADP+), 5.07 protein soluble ligase 4 chemokine 5.00 (C-X-C <0.0001 motif) receptor 5.03 2 <0.0001 0.0012 4.92 0.0013 <0.0001 0.60 <0.0001 0.0013 <0.0001 0.0015 0.0014 <0.0001 0.0017 4.92 0.59 0.69 <0.0001 4.94 0.0017 0.60 4.91 <0.0001 0.0017 0.65 4.78 0.65 <0.0001 0.0018 0.60 4.85 0.67 <0.0001 4.87 1.04 0.0022 4.85 <0.0001 4.77 <0.0001 4.83 0.0019 0.0018 0.68 <0.0001 <0.0001 0.0019 <0.0001 0.0022 0.002 4.77 <0.0001 0.0022

Confidential/Proprietary Information -44- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.74 4.760.62 <0.0001 4.76 0.0022 <0.0001 0.0022 0.63 4.37 <0.0001 0.0045 0.590.65 4.05 3.85 0.0002 0.0087 0.00040.72 0.0128 0.59 3.660.72-1.06 3.59-0.99 0.0008 3.14-0.75 -3.21 0.0184 0.0009 -3.21 0.0033 -3.22 0.0211 0.0027 0.0488 0.0027 0.0428 0.0026 0.0426 0.0418 NULL immunoglobulin lambda joining 2,immunoglobulin lambdavariable 2-14 joining 3,immunoglobulin lambda immunoglobulin lambda variable 2-14Diego blood group) TION WARNING ENTRY (H.sapiens) 0.63 3.70 0.0007 0.0169 167B5.2, OT- THUMG00000179513 IGLJ3, IGLJ3, IGLV2-14, IGLV2-14 IGLV2-14 Probe Set ID1556185_PM_a_at CTB- Gene Name220146_PM_at243824_PM_at Gene Description 204972_PM_at TLR7228280_PM_at LOC100996870 uncharacterized232958_PM_at LOC100996870 OAS2228190_PM_at ZC3HAV1L227426_PM_at toll-like receptor 7 235443_PM_at ATG4C zinc finger CCCH-type, antiviral 2’-5’-oligoadenylate213653_PM_at 1-like synthetase SOS1 2, 69/71kDa236583_PM_at LOC100131067 uncharacterized224989_PM_at LOC100131067 METTL3 autophagy related 4C, cysteine232000_PM_at peptidase GIMAP1 Homo sapiens son211163_PM_s_at cDNA of FLJ13595 sevenless fis, homolog clone 1 PLACE1009595 (Drosophila)216984_PM_x_at methyltransferase like 3 TNFRSF10C GTPase, IMAP family IGLJ2, member 1 IGLJ2, tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain202869_PM_at 0.65 Homo sapiens216050_PM_at cDNA FLJ13289 fis, clone Homo OVARC1001170 sapiens235643_PM_at cDNA FLJ11508 OAS1 fis, clone HEMBA1002162235306_PM_at 4.42231093_PM_at SAMD9L206978_PM_at GIMAP8 0.81 <0.0001 2’-5’-oligoadenylate206834_PM_at synthetase FCRL3 1, 40/46kDa 0.0043 0.63 0.67231956_PM_at sterile alpha CCR2 motif domain containing 9-like209995_PM_s_at 0.59 GTPase, HBD 4.76 IMAP family Homo member sapiens 8225207_PM_at cDNA: 4.70 FLJ20931 RNF213 fis, 4.67 TCL1A clone Fc ADSE01282 receptor-like 3 217148_PM_x_at 0.67 4.69 <0.0001 chemokine (C-C PDK4 motif) receptor IGLV2-14, 2 0.0022 0.61 <0.0001 0.66 <0.0001205592_PM_at ring hemoglobin, finger delta protein 0.0024 4.67 0.69 213 0.0026 T-cell leukemia/lymphoma 1A <0.0001 0.66238653_PM_at 0.0025 SLC4A1 4.60 4.65 pyruvate205950_PM_s_at dehydrogenase <0.0001 4.47 kinase, isozyme 4205067_PM_at 0.0026 4.44 0.64 CA1 <0.0001235086_PM_at <0.0001 solute carrier 0.60 0.003 family <0.0001 0.0027 4,237496_PM_at anion IL1B exchanger, member 0.0039 1 <0.0001 (erythrocyte 4.48 THBS1 membrane protein 0.0041 band 3, 4.59 carbonic anhydrase I <0.0001 0.68 0.75 interleukin 0.0038 1, thrombospondin beta <0.0001 1 0.59 0.003 4.33 4.26 ESTs, Weakly 4.09 similar to ALU7_HUMAN 0.0001 0.0001 ALU SUBFAMILY 0.60 SQ SEQUENCE CONTAMINA- 0.0049 0.0057 0.0002 0.77 0.0081 4.06 0.86 3.94 0.0002 0.60 3.75 0.0086 0.62 0.0003 3.78 0.0006 0.0107 3.83 0.0155 0.0005 0.0148 0.0005 0.0132

Confidential/Proprietary Information -45- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -1.02 -3.24 0.0025 0.0398 -1.02-0.59 -3.40 -3.49 0.0016-0.71 0.0012 0.0298 0.0256 -3.53 0.0011 0.0237 -0.86-0.80 -3.71 -3.77 0.0007 0.0168 -0.80 0.0006-1.00 0.0149 -3.85 -3.88-0.61 0.0004 0.0004 0.0129 -3.91 0.0121 -0.73 0.0004 0.0114 -3.95 0.0003 0.0107 TION WARNING ENTRY (H.sapiens) Probe Set ID39402_PM_at1569477_PM_at230380_PM_at Gene Name IL1B207075_PM_at244840_PM_x_at THAP2 Gene Description 203504_PM_s_at NLRP3 DOCK4209774_PM_x_at ABCA1 interleukin 1,205220_PM_at beta CXCL2 THAP domain containing,240038_PM_at apoptosis associated Homo protein sapiens, NLR 2 clone dedicator family, pyrin IMAGE:4291396, of domain mRNA201466_PM_s_at cytokinesis containing HCAR3 4 3 ATP-binding cassette,218856_PM_at sub-family A (ABC1), JUN member 1 chemokine215630_PM_at (C-X-C motif) ligand 2201340_PM_s_at TNFRSF21 hydroxycarboxylic acid receptor 3241740_PM_at ENC1 tumor necrosis jun factor receptor proto-oncogene 1564430_PM_at superfamily, member 21233674_PM_at233127_PM_at ectodermal-neural cortex 1 (with BTB238756_PM_at domain) Homo sapiens225955_PM_at cDNA FLJ14102 fis, clone MAMMA1000940212158_PM_at -0.63 GAS2L3 ESTs, Moderately similar1554980_PM_a_at to METRNL ALU7_HUMAN ALU SUBFAMILY SQ SEQUENCE CONTAMINA- 239827_PM_at ATF3 SDC2 Homo -3.25 sapiens, clone IMAGE:2960704, -0.66 mRNA1557166_PM_at growth arrest-specific -0.60 2 Homo like sapiens 3 meteorin,37028_PM_at cDNA: glial FLJ22633 RGCC cell fis, differentiation clone Homo regulator-like HSI06502 0.0024 sapiens PDCD4240024_PM_at cDNA FLJ12412 -3.32 fis, clone MAMMA1003004 -3.25 syndecan activating 0.0396 218880_PM_at 2 transcription factor -0.62 3 PPP1R15A235592_PM_at SEC14L2 -0.64 0.002 regulator of224836_PM_at programmed cell cell FOSL2 0.0024 cycle death 4 protein -3.25 (neoplastic phosphatase transformation202637_PM_s_at 1, inhibitor) regulatory 0.0348 subunit 0.0396 15A -3.51 -0.93 SEC14-like -0.76 21561882_PM_at (S. TP53INP2 cerevisiae) -0.74 ICAM1202988_PM_s_at 0.0024 -0.73 FOS-like antigen SYTL3 2 202638_PM_s_at 0.0012 -3.32 -3.31 0.0391 RGS1 tumor -0.60 protein -3.52 p53203505_PM_at inducible nuclear 0.0246 protein ICAM1 -3.37 2 intercellular207113_PM_s_at adhesion molecule 1 0.002 0.0021564093_PM_at -3.53 0.0011 ABCA1 synaptotagmin-like 3 TNF 0.0017208869_PM_s_at 0.0347 0.0354 regulator of 0.0239 -0.68 G-protein signaling NEK1 1 intercellular1554836_PM_at adhesion 0.0318 molecule 0.0011 -0.61 1 -0.63 GABARAPL1231972_PM_at ATP-binding cassette, 0.0238 sub-family -3.65 USP36 A GABA(A) (ABC1), receptor-associated -0.63 member -0.73 protein 1 like tumor 1 -3.55 necrosis -3.54 factor NIMA-related kinase 1 0.0008 -3.68 -3.78 0.0011 ubiquitin 0.0011 specific 0.0187 peptidase 36 -0.71 0.0229 0.0234 0.0007 0.0005 -0.67 0.0175 0.0148 -0.76 Homo -3.66 sapiens cDNA: FLJ21028 fis, -3.80 clone CAE07155 -3.73 0.0008 -0.72 0.0005 0.0184 0.0142 -0.60 0.0006 -3.90 0.0162 -0.63 -3.80 -0.76 0.0004 -3.94 0.0116 0.0005 -0.62 -3.91 -0.81 -0.76 0.014 0.0003 -3.97 0.0107 0.0004 -3.92 -3.94 0.0116 -0.76 0.0003 0.0004 0.0003 0.0102 0.0111 -4.00 0.0108 -0.60 -0.78 0.0003 -3.97 -3.96 0.0097 0.0003 0.0003 0.0102 0.0105

Confidential/Proprietary Information -46- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.60 -4.07 0.0002 0.0084 -0.78 -4.23-0.62 0.0001 0.0061 -4.26 0.0001-0.65 0.0056 -4.32-0.61 0.0001 0.005 -4.36-0.98 <0.0001 0.0046 -4.38 <0.0001 0.0045 -0.59 -4.43 <0.0001 0.0042 DNA-directed RNA polymerase IIIpolypeptide subunit E RPC5-like,polymerase (80kD) (RNA) III (DNA directed) NULL POLR3E RP1-239B22.5 Probe Set ID202437_PM_s_at210258_PM_at CYP1B1212659_PM_s_at Gene Name201195_PM_s_at RGS13 IL1RN231484_PM_at Gene cytochrome Description SLC7A5 P450, family 1,219312_PM_s_at subfamily B, polypeptide 1226034_PM_at regulator ZBTB10 of G-protein204363_PM_at signaling interleukin 13 1 receptor solute antagonist carrier family216243_PM_s_at 7 DUSP4 (amino acid transporter light chain,226397_PM_s_at L F3 system), IL1RN member zinc 5 finger and232406_PM_at BTB domain containing 101565776_PM_at dual specificity phosphatase 41562255_PM_at36711_PM_at interleukin 1 receptor antagonist SYTL3 coagulation244578_PM_at factor III (thromboplastin, tissue -0.80 factor)204103_PM_at MAFF Homo233458_PM_at sapiens LCP2 cDNA: FLJ21028 fis, clone CAE07155 -4.05 CCL4 synaptotagmin-like 3 Homo sapiens -0.72202435_PM_s_at cDNA FLJ13731 LOC101060521, Homo fis, sapiens clone mRNA; PLACE3000142 cDNA209967_PM_s_at DKFZp667M067 (from v-maf clone musculoaponeurotic 0.0002 CYP1B1 DKFZp667M067) fibrosarcoma oncogene homolog lymphocyte202436_PM_s_at F cytosolic -4.00 (avian) protein CREM 2 0.0088 (SH2 domain chemokine240207_PM_at containing (C-C leukocyte motif) protein ligand CYP1B1 of 4 76kDa)204014_PM_at cytochrome 0.0003 P450, family 1,233309_PM_at subfamily B, polypeptide 1 0.0096 205193_PM_at cAMP responsive DUSP4 element cytochrome modulator P450, family 1,229715_PM_at subfamily -0.59 B, -0.75 polypeptide -0.62 1 MAFF -0.62 -0.771554096_PM_a_at OTTHUMG00000173015, dual -4.01 specificity -4.20 phosphatase -4.24 -0.62 4206173_PM_x_at -1.02 RBM33 -4.02 -4.08243659_PM_at -0.89 GABPB1 -0.81 v-maf 0.0003202014_PM_at musculoaponeurotic 0.0002 fibrosarcoma 0.0001 -4.11 -4.23 oncogene homolog Homo F sapiens (avian) 0.0003202068_PM_s_at cDNA 0.0002 FLJ11759 0.0095 -0.82 0.0064 RNA fis, binding 0.0059 clone motif HEMBA1005616 -4.19 protein1554906_PM_a_at 33 -4.20 0.0093 PPP1R15A -0.60 GA 0.0083 binding LDLR protein 0.0002 0.0001 transcription203394_PM_s_at factor, MPHOSPH6 beta subunit 1 -4.11 0.0077 0.006 1555638_PM_a_at 0.0002 protein phosphatase HES1 0.0002 -4.11 1, M-phase regulatory217127_PM_at phosphoprotein subunit SAMSN1 6 15A 0.0067 0.0065 -0.71 0.0002202933_PM_s_at low density lipoprotein receptor 0.0002214230_PM_at 0.0077 CTH YES1 SAM -0.70215485_PM_s_at domain, 0.0077 SH3 hairy -4.29 domain and and enhancer -1.02 nuclear of localization split signals 1, CDC42 1 (Drosophila) ICAM1 -4.30 0.0001 -0.87 -4.36 v-yes-1 cystathionase Yamaguchi (cystathionine sarcoma gamma-lyase) viral -1.05 0.0054 oncogene homolog 1 cell 0.0001 -0.66 division cycle intercellular -4.25 42 adhesion molecule <0.0001 1 0.0052 -4.30 0.0047 -4.34 0.0001 -0.65 0.0001 0.0058 -0.66 0.0001 0.0053 -4.38 0.0049 -4.33 -0.89 -0.77 <0.0001 0.0045 -0.61 0.0001 -4.40 -4.39 0.0049 -4.37 -0.65 <0.0001 <0.0001 -0.77 0.0043 0.0045 -0.62 -0.65 <0.0001 -4.41 -0.78 0.0045 -4.40 -4.39 -4.39 <0.0001 -4.41 <0.0001 0.0043 <0.0001 <0.0001 0.0044 0.0044 0.0044 <0.0001 -0.60 0.0043 -4.44 <0.0001 0.0041

Confidential/Proprietary Information -47- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.64 -4.48-1.15-0.86 <0.0001 -4.50 0.0038 -4.51-0.77 <0.0001 0.0037 <0.0001 -4.53 0.0036 <0.0001 0.0034 -0.88-0.69 -4.64 -4.66 <0.0001 0.0027 <0.0001 0.0027 -0.92 -4.70 <0.0001 0.0025 -0.61 -4.74-0.61 <0.0001 0.0023 -4.77 <0.0001 0.0022 NULL RP11- 769O8.3 Probe Set ID201631_PM_s_at204790_PM_at IER3237204_PM_at Gene Name216350_PM_s_at SMAD7206983_PM_at Gene Description ZNF101570432_PM_at immediate early response230233_PM_at 3 CCR6 SMAD family member 7201465_PM_s_at zinc1553266_PM_at finger protein 10 JUN230511_PM_at ESTs, Moderately CNOT6L chemokine similar227140_PM_at (C-C to motif) OVCA1 receptor 6202932_PM_at CREM1564150_PM_a_at INHBA Homo sapiens clone jun CCR4-NOT pp10199 transcription proto-oncogene 202684_PM_s_at unknown complex, C12orf79 subunit mRNA. YES1 6-like218631_PM_at RNMT cAMP responsive233952_PM_s_at element modulator inhibin, beta chromosome A 1560485_PM_at 12 open AVPI1 reading ZBTB21 frame 79 v-yes-1230652_PM_at Yamaguchi sarcoma viral oncogene homolog HIVEP1 1206157_PM_at RNA (guanine-7-) methyltransferase217996_PM_at ARAF zinc finger arginine and vasopressin-induced222180_PM_at BTB 1 PTX3 domain containing 21 human immunodeficiency PHLDA1 virus type I enhancer binding OTTHUMG00000178354, protein 1 v-raf209325_PM_s_at murine sarcoma 3611 viral oncogene homolog pentraxin219228_PM_at pleckstrin 3, homology-like long domain, RGS16 family A, member227099_PM_s_at 1 -0.86244054_PM_at ZNF331 C11orf96207630_PM_s_at -0.64 -0.67 regulator -0.69 of -0.71225539_PM_at G-protein -4.45 signaling CREM 16 -0.63230218_PM_at chromosome zinc 11 finger open protein -4.51 -4.49 reading 331 frame -0.81212722_PM_s_at 96 ZBTB21 -4.46 -4.46 <0.0001223787_PM_s_at -4.49 HIC1 0.004 JMJD6 -0.61226833_PM_at cAMP <0.0001 <0.0001 responsive -4.55 element -1.12 CCDC174 modulator <0.0001 <0.0001 0.0036 0.0037 242058_PM_at -0.96 zinc finger 0.0039 0.0039 <0.0001 and BTB -4.62 domain233899_PM_x_at containing CYB5D1 21 0.0037 <0.0001 -4.51 jumonji coiled-coil204491_PM_at domain domain hypermethylated containing in containing 6 cancer 174 ZBTB10 0.0033 -4.57 1 -0.66242727_PM_at <0.0001 -0.70 -0.75241970_PM_at cytochrome 0.0029 <0.0001 PDE4D b5 domain containing -1.47 1 <0.0001213638_PM_at 0.0036 -4.59 ARL5B zinc finger 0.0031 -4.62 and -0.73 BTB domain -4.63 containing 10 -4.66 PHACTR1 phosphodiesterase <0.0001 4D, cAMP-specific <0.0001 0.003 -4.59 ADP-ribosylation <0.0001 factor-like 5B 0.0029 <0.0001 0.0028 phosphatase and actin regulator 1 0.0027 <0.0001 0.003 -0.60 -0.74 -4.67 -4.70 -1.18 -0.75 <0.0001 -1.18 <0.0001 0.0026 -4.71 0.0025 -4.71 -4.69 -0.59 <0.0001 <0.0001 -0.63 0.0024 -0.71 -0.61 -0.82 0.0024 <0.0001 -4.73 0.0025 -4.72 -0.72 -4.73 -4.72 -4.77 <0.0001 0.0024 <0.0001 -4.77 <0.0001 <0.0001 <0.0001 0.0024 0.0023 0.0024 0.0022 -0.79 -1.09 <0.0001 0.0022 -4.77 -4.78 <0.0001 <0.0001 0.0022 0.0022

Confidential/Proprietary Information -48- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.59 -4.93-0.82 <0.0001 0.0017 -4.97 <0.0001 0.0016 -0.73 -5.17 <0.0001 0.0011 SFT2 domain containing 3,WD repeat domain 33 -0.73 -5.46 <0.0001 0.0007 WDR33 Probe Set ID220612_PM_at214508_PM_x_at223767_PM_at Gene Name CREM209803_PM_s_at223915_PM_at GPR84 Gene Description PHLDA2237718_PM_at1553785_PM_at cAMP responsive BCOR element modulator240103_PM_at EIF4E pleckstrin G homology-like Homo protein-coupled domain, sapiens RASGEF1B receptor family243771_PM_at PRO0641 84 A, protein member (PRO0641), 2 mRNA.210837_PM_s_at LOC100996457 BCL6 RasGEF corepressor domain uncharacterized215072_PM_x_at family, LOC100996457 member 1B PDE4D eukaryotic206683_PM_at translation initiation factor C10orf137 4E201712_PM_s_at1554095_PM_at ZNF165 RANBP2 phosphodiesterase chromosome 4D,203395_PM_s_at 10 cAMP-specific open reading frame 137 RBM33224098_PM_at HES1236646_PM_at zinc RAN finger binding protein protein 165 2226982_PM_at210004_PM_at RNA TMEM52B binding motif protein 33211423_PM_s_at ELL2 hairy and enhancer of split226922_PM_at 1, OLR1 (Drosophila) SC5D transmembrane protein 52B213452_PM_at -1.01 -0.66228749_PM_at RANBP2 Homo sapiens201489_PM_at PRO1546 elongation mRNA, ZNF184 factor, complete RNA -4.88 -4.78 cds. polymerase II, -1.04 oxidized 2233121_PM_at low sterol-C5-desaturase ZDBF2 density lipoprotein (lectin-like) receptor 1204567_PM_s_at RAN binding PPIF protein 2 <0.0001 <0.0001217999_PM_s_at -4.80 zinc finger ABCG1 0.0018 0.0022 protein 1841557049_PM_at -0.74 PHLDA1 zinc finger, DBF-type -1.14 -1.15227613_PM_at containing 2 <0.0001 -1.22 BTBD191552711_PM_a_at peptidylprolyl 0.0021 isomerase F -4.85 ATP-binding cassette, sub-family201490_PM_s_at CYB5D1 G ZNF331 -4.94 -4.95 (WHITE), pleckstrin member homology-like 1 domain, -0.66 family -0.96211434_PM_s_at -4.95 A, member 1 PPIF Homo BTB sapiens (POZ)223394_PM_at <0.0001 cDNA domain FLJ12299 containing fis, CCRL2 19 clone <0.0001 <0.0001 MAMMA1001851 0.0019 cytochrome217998_PM_at b5 -5.00 zinc -5.00 domain <0.0001 finger 0.0017 0.0016 containing protein 1 331204541_PM_at 0.0016 SERTAD1238693_PM_at PHLDA1 peptidylprolyl <0.0001 isomerase <0.0001 chemokine F (C-C207826_PM_s_at -0.79 motif) SEC14L2 receptor-like 0.0015 2 0.0015 SERTA domain containing231779_PM_at 1 PHC3 -1.56 ID3 -0.61218851_PM_s_at pleckstrin homology-like -0.60 -0.66 -0.63 domain, -5.07 family A, SEC14-like member 2 1 (S. IRAK2 cerevisiae) SFT2D3, -5.16 -5.08 -0.87 -5.01 -0.63 -5.06 -5.02 <0.0001 polyhomeotic homolog 3 (Drosophila) 0.0013 inhibitor of <0.0001 DNA -0.69 <0.0001 binding 3, interleukin-1 dominant -5.13 receptor-associated 0.0011 negative <0.0001 -5.09 <0.0001 kinase <0.0001 helix-loop-helix 0.0013 2 protein -1.02 0.0014 0.0013 0.0014 -0.98 -5.28 <0.0001 <0.0001 -5.27 0.0012 0.0012 -0.65 -5.32 -0.59 <0.0001 0.0009 <0.0001 -0.70 -5.22 <0.0001 0.0009 -5.18 0.0008 -0.76 -5.18 -0.85 <0.0001 -0.64 -0.67 -1.02 <0.0001 0.001 -5.22 0.001 <0.0001 -5.34 -0.94 -5.37 -5.46 0.001 -5.44 <0.0001 -1.39 0.001 <0.0001 -5.43 <0.0001 <0.0001 -0.87 0.0008 <0.0001 0.0007 -0.80 0.0007 0.0007 -5.37 <0.0001 -0.61 -5.41 -0.64 0.0007 -0.59 -5.43 <0.0001 -5.46 0.0008 <0.0001 -5.46 -5.44 <0.0001 0.0007 0.0007 <0.0001 <0.0001 <0.0001 0.0007 0.0007 0.0007

Confidential/Proprietary Information -49- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.74 -5.52 <0.0001 0.0006 -0.71 -5.65 <0.0001 0.0005 -0.78 -5.75 <0.0001 0.0005 -0.91 -5.95 <0.0001-0.60 0.0003 -0.66 -6.08 -6.08 <0.0001 0.0003 <0.0001 0.0003 NULL RP11- 425D10.10 Probe Set ID210836_PM_x_at1556499_PM_s_at PDE4D216066_PM_at COL1A1 Gene Name204435_PM_at241985_PM_at ABCA1 Gene Description phosphodiesterase 4D,223484_PM_at collagen, cAMP-specific NUPL1 type I, alpha 1207850_PM_at JMY204614_PM_at C15orf48 ATP-binding cassette, sub-family A217997_PM_at (ABC1), CXCL3 member 1 nucleoporin like 1 205479_PM_s_at SERPINB2 chromosome209959_PM_at 15 PHLDA1 open junction reading mediating PLAU frame and 48 regulatory227093_PM_at protein, p53 serpin cofactor chemokine peptidase (C-X-C inhibitor, motif) clade226099_PM_at ligand B NR4A3 3 (ovalbumin), member 2219557_PM_s_at pleckstrin USP36 homology-like domain, family A, member228536_PM_at 1 ELL2 plasminogen activator, NRIP3 urokinase223028_PM_s_at nuclear receptor subfamily232081_PM_at 4, PRMT10 group A, SNX9 ubiquitin member specific 3 peptidase203835_PM_at 36207978_PM_s_at nuclear elongation receptor ABCG1 factor, interacting RNA protein polymerase 3 II, 2224978_PM_s_at protein LRRC32 arginine methyltransferase NR4A3 10 (putative)211840_PM_s_at sorting nexin USP36 9 -0.75208115_PM_x_at ATP-binding cassette, PDE4D sub-family G -0.85239835_PM_at (WHITE), leucine member rich 1 repeat C10orf137 containing nuclear 32 receptor204015_PM_s_at -5.50 subfamily 4, -0.88 group A, -1.79 ubiquitin member1556676_PM_a_at specific 3 KBTBD8 peptidase -5.49 36 DUSP4 phosphodiesterase chromosome 4D, 10 cAMP-specific OTTHUMG00000175937, open <0.0001 reading frame 137 -5.52 -5.54 0.0006 <0.0001 -1.54 -0.831554290_PM_at kelch repeat -1.48 and 0.0006 BTB dual (POZ) specificity domain225842_PM_at phosphatase containing <0.0001 4 8 <0.0001 HERC3227029_PM_at 0.0006 -5.58 -5.50 0.0006 -5.531563505_PM_at PHLDA1 -1.33 -2.16223887_PM_at FAM177A1 <0.0001 <0.0001 DUSP16244868_PM_at <0.0001 HECT and 0.0005 0.0006 RLD domain containing 0.0006 -5.54 -5.61 E3 -0.74212750_PM_at pleckstrin ubiquitin GPR132 homology-like protein family domain, ligase with family sequence 3 A, similarity member -0.76242040_PM_at 177, -0.68 1 member A1 dual specificity224979_PM_s_at phosphatase PPP1R16B <0.0001 <0.0001 16 -5.60 -0.98205476_PM_at -1.29 0.0006 0.0005 G GCNT7 protein-coupled -0.73 -5.64 -5.67 receptor USP36 132212086_PM_x_at protein phosphatase 1, <0.0001 -2.15 regulatory -5.62238645_PM_at subunit CCL20 16B -5.63 LMNA 0.0005 -5.62 <0.0001 <0.0001 glucosaminyl 0.0005 (N-acetyl) 0.0005 transferase ubiquitin family specific member -5.70 peptidase <0.0001 7 36 <0.0001 <0.0001 0.0005 -0.65 0.0005 chemokine (C-C 0.0005 -0.67 motif) -0.76 -0.78 lamin ligand A/C 20 <0.0001 -0.65 0.0005 -0.87 -5.67 -5.72 -5.73 -5.72 -5.77 -5.71 <0.0001 <0.0001 <0.0001 <0.0001 -1.13 0.0005 0.0005 -0.82 0.0005 0.0005 <0.0001 <0.0001 -0.75 0.0004 -5.78 0.0005 -5.75 -5.81 <0.0001 <0.0001 0.0004 -0.62 -0.64 0.0005 <0.0001 0.0004 -0.62 -5.98 -6.00 -0.81 -5.82 <0.0001 <0.0001 -5.85 0.0003 0.0003 <0.0001 -0.68 0.0004 <0.0001 -2.03 0.0004 -6.03 -6.07 <0.0001 0.0003 <0.0001 0.0003

Confidential/Proprietary Information -50- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.62-0.90 -6.14 -6.24 <0.0001-1.98 0.0002 <0.0001 -6.33 0.0002 <0.0001 0.0002 -1.01 -6.52-1.15 <0.0001 -6.94 0.0002 -1.47 <0.0001 -8.34 <0.0001 <0.0001 <0.0001 FC t-Statistic P FDR 2 Log 0.790.79 6.52 6.52 <0.0001 0.0003 <0.00010.95 0.0003 0.95 5.83 5.83 <0.0001 0.0009 <0.0001 0.0009 Differentially expressed genes (Combined Study Groups, Day 0 vs. 14). Sorted by descending t-statistic. Probe set annotations were Gene NamePARP9GBP1OTTHUMG00000159342 RP1-93H18.6 GBP4 Gene Description EPSTI1GBP5 poly (ADP-ribose) polymerase family,STAT1 member 9 guanylate bindingAIM2 protein 1, interferon-inducibleFCGR1B FCGR1C guanylate bindingIFI44L protein epithelial 4 stromal interaction 1SERPING1 (breast) guanylate bindingDDX60 protein 5 signal transducer andIFIT2 activator of transcription 1, 91kDa absent in melanoma 2 serpin peptidase inhibitor, interferon-induced clade protein G 44-like (C1 inhibitor), member 1 DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 interferon-induced protein 0.69 with tetratricopeptide repeats 2 1.14 6.80 6.54 0.74 <0.0001 0.0003 <0.0001 0.72 6.03 0.0003 0.99 6.13 0.75 5.68 <0.0001 0.0007 0.76 0.79 6.48 <0.0001 0.59 <0.0001 0.0007 5.33 6.10 0.0012 0.63 0.88 <0.0001 5.40 0.0003 5.79 <0.0001 <0.0001 5.95 0.0022 0.0007 <0.0001 0.002 <0.0001 <0.0001 0.001 0.0007 Probe Set ID206648_PM_at203411_PM_s_at215501_PM_s_at ZNF571 Gene Name LMNA239567_PM_at DUSP10222900_PM_at Gene Description 204087_PM_s_at zinc finger protein 571210118_PM_s_at lamin NRIP3 A/C dual SLC5A6 specificity phosphatase 10220370_PM_s_at IL1A205330_PM_at USP36221563_PM_at solute carrier nuclear family receptor1565868_PM_at 5 interacting MN1 (sodium-dependent protein vitamin 3 transporter), member 6209383_PM_at DUSP10 interleukin 1, CD44 ubiquitin alpha 239876_PM_at specific peptidase 36206374_PM_at DDIT3206404_PM_at dual meningioma specificity (disrupted phosphatase in 10 balanced translocation)209270_PM_at 1 DUSP8 CD44 molecule (Indian1555279_PM_at blood FGF9 group) DNA-damage-inducible transcript209324_PM_s_at 3 LAMB3 -0.71 ARMC8239451_PM_at dual RGS16 specificity phosphatase 8 fibroblast -6.32 growth factor 9 laminin, (glia-activating beta factor) 3 armadillo repeat containing 8 regulator of G-protein signaling <0.0001 16 0.0002 -0.70 -1.00 -0.87 -6.18 -0.93 -6.13 -6.29 <0.0001 -6.38 0.0002 -0.82 <0.0001 <0.0001 0.0002 <0.0001 0.0002 -0.66 -0.77 0.0002 -6.35 -1.04 -0.84 -6.40 -6.49 <0.0001 0.0002 -6.51 -6.83 <0.0001 -0.73 <0.0001 0.0002 0.0002 <0.0001 <0.0001 0.0002 -1.04 -6.71 0.0001 -0.68 -7.41 <0.0001 -7.15 0.0001 <0.0001 <0.0001 <0.0001 <0.0001 Table 77: obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Confidential/Proprietary Information -51- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.76 4.91 <0.0001 0.0046 -0.60-0.60 -4.13 -4.13-0.73 0.0002 0.0002 -4.42 0.0174 0.0174 <0.0001 0.0112 Gene NameGBP1P1SAMD9LWARSIFIT3SMCO4 Gene Description TNFSF10MYOF guanylate binding protein 1, interferon-inducible pseudogene sterileIFI35 1 alpha motif domain containing 9-likeCXCL10 tryptophanyl-tRNA synthetaseANKRD22IFIT1 interferon-induced protein single-pass with membrane tetratricopeptide protein tumor repeats with necrosis 3 coiled-coilTFEC factor domains (ligand) 4 superfamily, member 10LOC284837 myoferlin OAS1ZNF331 interferon-induced chemokine protein (C-X-C 35 motif) ankyrin ligand repeat 10 domainCCL20 22C12orf79 0.83NR4A3 uncharacterized interferon-induced LOC284837 protein with tetratricopeptide repeats transcription 1GPR84 factor ECOTTHUMG00000178354 5.25 2’-5’-oligoadenylate synthetaseRP11-769O8.3 1, zinc 40/46kDa finger protein 331C15orf48 chemokine (C-C chromosome motif)ZNF571 12 ligand open 0.74 20 reading frame <0.0001 79 0.59IL1A 0.80 nuclear 0.0023 receptor subfamily 4,SERPINB2 0.81 group A, G member protein-coupled 3 receptor 5.05 84CYP1B1 4.97 5.25PMP22 4.95 chromosomeCCRL2 15 open reading frame 48SERTAD1 0.61 <0.0001 zinc finger protein <0.0001 571 0.0035 C11orf96 <0.0001 0.74 serpin 0.0042 peptidase inhibitor, <0.0001 cladeMN1 0.0023 B (ovalbumin), interleukin member 1, 2 alpha 5.19 0.0043 OLR1 cytochrome P450, family 1, subfamily 4.43 B,PRMT10 polypeptide 1 peripheral myelin 1.08 protein 22CYB5D1 chemokine SERTA (C-C domain motif) containing <0.0001 receptor-like 1CTH 0.59 2 0.0026 chromosomeSMAD7 <0.0001 11 open 4.71 reading 0.59 frame 0.87 96 0.011 PHLDA1 4.72 0.68NRIP3 meningioma (disrupted in balanced oxidized translocation) protein lowFAM177A1 1 3.63 arginine density 4.47 methyltransferase lipoprotein -0.97 10 <0.0001 (lectin-like) (putative) receptor 1 cytochrome b5 -0.62 0.0068 3.99 domain containing 0.67 1 <0.0001 0.0068 -3.92 -1.29 cystathionase SMAD 0.0009 (cystathionine <0.0001 family gamma-lyase) -3.84 member -1.23 7 pleckstrin homology-like -0.72 0.01 4.32 domain, family 0.0449 0.0003 A, member 1 -3.72 family with sequence nuclear 0.0222 0.0004 similarity receptor interacting 177, -4.42 protein member -0.64 -0.97 3 A1 -0.59 0.0005 -3.59 0.0256 0.0001 0.0295 0.0007 -4.06 -4.24 0.0131 -4.64 <0.0001 0.0379 0.001 0.0112 0.0472 0.0002 0.0001 <0.0001 -0.64 0.0075 0.0194 0.0149 -0.77 -0.72 -1.48 -0.68 -4.34 -0.62 -0.66 -5.32 -4.74 -5.37 -0.62 -5.25 -4.66 -5.43 0.0001 -0.95 -5.10 <0.0001 <0.0001 <0.0001 0.0129 -0.62 0.0022 -0.65 0.0065 0.002 <0.0001 -5.95 <0.0001 <0.0001 0.0023 -0.65 0.0073 0.002 <0.0001 -5.76 -5.54 0.0032 -6.39 <0.0001 -0.97 0.0007 <0.0001 <0.0001 -0.70 0.001 0.0016 <0.0001 -5.96 0.0004 -5.84 <0.0001 0.0007 <0.0001 0.0009

Conﬁdential/Proprietary Information -52- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold 2 log FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log -1.03 -6.88 <0.0001 0.0003 Log 0.78 5.21 <0.0001 0.0015 0.67 4.34 0.0001 0.0065 -0.74 -3.77 0.0006 0.0166 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tularemia), Day 2 vs. 0). The average Gene NameLAMB3DDIT3 Gene Description laminin, beta 3 DNA-damage-inducible transcriptGene 3 NameRRM2MS4A14KIAA0101METTL3TFEC Gene Description AIM2HDHD2 ribonucleotide reductaseSAMD9L membrane-spanning M2 4-domains, subfamily A, KIAA0101 member 14ATP10DPAQR8 methyltransferase like 3SLC38A9 transcriptionC9orf69 factor ECTLR5 absent in haloacid melanoma dehalogenase-like 2 hydrolase domain sterile containingGAPT alpha 2 motif domain containing 9-likeTNFSF10 ATPase, class V, type 10DGIMAP4 progestin and adipoQ solute receptor carrierLOC284837 family family member 38, VIII member 9 -0.92MS4A7 chromosome 9 open reading frameOAS1 69 toll-likeTCL1A -6.95 receptor 0.68 5 tumor GRB2-binding necrosis adaptorCCR2 factor protein, (ligand) transmembrane superfamily, member 10ATG4C uncharacterized GTPase, LOC284837 IMAP family member 4 5.73TNFRSF17 <0.0001 0.0003 TNFAIP6 membrane-spanning 4-domains, subfamily A,HCAR3 member 0.61 7 2’-5’-oligoadenylate <0.0001 synthetaseCCL4 1, 40/46kDa T-cell leukemia/lymphoma 1A 0.0005 NAMPT 4.70 chemokine 0.83 (C-CMETRNL motif) tumor receptor autophagy necrosis 2 related factor 4C, receptor cysteine superfamily,PTX3 member peptidase 17 tumorPPP1R15A necrosis factor, alpha-induced 5.95 0.68 protein 6 0.71 <0.0001IER3 hydroxycarboxylic 0.60 acid receptor 0.0033 3 chemokine 4.64 (C-C motif) nicotinamide ligand 4.51 phosphoribosyltransferase <0.0001 4 0.63 meteorin, 0.59 5.20 glial cell 0.0004 differentiation regulator-like 0.67 protein phosphatase 0.63 1, 0.60 regulatory pentraxin 0.60 0.62 subunit 3, 15A <0.0001 5.05 long 4.25 <0.0001 0.62 0.0038 <0.0001 0.0048 4.76 0.0015 immediate 4.26 4.49 early response 4.42 4.56 3 <0.0001 4.07 0.0001 0.0018 <0.0001 0.0078 0.62 0.61 0.0001 <0.0001 0.61 0.0031 <0.0001 <0.0001 0.70 0.0049 0.0058 0.0076 0.0044 0.0002 3.41 0.0102 4.19 3.96 4.12 0.61 -0.70 0.71 0.59 0.0016 0.0002 0.0003 3.74 0.0002 -3.21 0.0314 0.0085 0.0123 0.0097 3.84 -0.61 3.82 -0.63 -0.62 -0.68 0.0027 0.0006 -3.75 0.0439 0.0174 0.0005 -3.41 -3.24 -0.70 0.0005 -3.91 0.0149 0.0155 0.0006 -3.35 0.0016 0.0025 0.017 0.0004 0.0313 0.042 0.0129 0.0019 -0.64 0.0349 -3.95 0.0003 0.0123 change was used toannotations were combine obtained probe from Affymetrix sets (HT with HG-U133 Plus the PM same Annotations, Release gene 34,10/24/13). symbol prior to the analysis. Results are sorted by descending t-statistic. Gene Table 78:

Confidential/Proprietary Information -53- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.60-0.60 -4.01 -4.01-0.65-0.65 0.0003 0.0003 -4.12 0.0114 -4.12 0.0114 0.0002 0.0002 0.0097 -0.74 0.0097 -0.87 -4.43 -4.49 <0.0001 0.0055 <0.0001 0.0049 -0.62 -4.78 <0.0001 0.003 -0.66-0.66 -5.12 -5.12-0.76 <0.0001 0.0017 <0.0001 0.0017 -5.42 <0.0001 0.001 Gene NameARL5BMIR155 MIR155HG CXCL3C12orf79 Gene Description OTTHUMG00000184015 RP6-99M1.2 ADP-ribosylation factor-like 5BICAM1MAP3K8TP53INP2 chemokine (C-X-C motif) chromosome ligandMAFF 12 3 open reading frame 79F3IL1ATHBD intercellular adhesion molecule mitogen-activatedCCR6 1 protein kinase kinase tumor kinase protein 8 p53CREM inducible nuclear protein 2GABARAPL1 v-maf musculoaponeuroticDUSP4 fibrosarcoma oncogene homolog F (avian)PHACTR1 coagulation factorABCA1 III interleukin (thromboplastin, 1, tissue alpha factor) thrombomodulin YES1 GABA(A) chemokine receptor-associated (C-CRNMT protein motif) like receptor 1 6 cAMP responsive elementCCL20 modulatorZBTB21 dual phosphatase specificity and phosphatase actin 4MAFB regulator 1SIK3 ATP-binding cassette, -0.97 sub-family A -0.68CYP1B1 (ABC1), member 1 v-yes-1AVPI1 Yamaguchi sarcoma -0.68 viral oncogene RNA homolog (guanine-7-) 1 -4.40RASGEF1B methyltransferase -4.01 -1.08 chemokine -0.62 (C-C motif)ZNF331 ligand zinc 20 finger and -4.09 BTB domainPDCD4 containing 21 -0.80 v-maf -4.02 musculoaponeurotic <0.0001C11orf96 -4.17 fibrosarcoma 0.0003 oncogene homolog B 0.0059 (avian)MPHOSPH6 cytochrome SIK P450, family family 0.0114 kinase -0.67 1, 0.0002 3 subfamily -0.65 B, -4.18OTTHUMG00000175937 RasGEF polypeptide domain 1 family, member 1B arginine 0.0003 0.01 vasopressin-inducedRP11-425D10.10 0.0002 1 -4.17SLC7A5 0.0112 zinc 0.0089 -4.41 finger protein 331 0.0002KBTBD8 programmed cell death -0.64 chromosome M-phase 4JMY 11 phosphoprotein (neoplastic 0.0088 open 6 transformation reading inhibitor) frame 96 0.0002RGCC <0.0001 -0.63 0.0089 0.0058 -4.52 -0.66 -0.68 -0.59 -0.66 -4.63 solute carrier family 7 -4.51 (amino -4.76 kelch acid -4.49 <0.0001 repeat transporter -4.68 -0.87 and light BTB chain, (POZ) L domain system), 0.0048 containing -0.74 member 8 5 <0.0001 junction mediating and -4.60 regulator 0.0039 <0.0001 regulatory of <0.0001 cell protein, <0.0001 cycle p53 <0.0001 cofactor -0.62 -4.53 -0.66 0.0048 0.0031 0.0049 -0.66 0.0034 <0.0001 -0.82 -1.64 -4.72 -4.90 -0.96 -4.72 0.0041 <0.0001 0.0047 -5.03 -4.72 -5.20 <0.0001 <0.0001 -0.90 <0.0001 0.0032 0.0024 0.0032 -0.62 <0.0001 <0.0001 -4.99 <0.0001 0.0019 0.0032 -0.74 0.0015 -4.93 <0.0001 -5.05 -0.77 -1.14 -0.71 0.002 -0.90 <0.0001 0.0023 -5.38 <0.0001 -4.99 -5.10 -5.41 0.0018 <0.0001 <0.0001 <0.0001 <0.0001 0.0011 0.002 0.0017 0.001

Confidential/Proprietary Information -54- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold 2 log FC t-Statistic P FDR 2 Log -1.15-0.75-0.75 -6.51 -6.53 -6.53 <0.0001 0.0002 <0.0001 0.0002 <0.0001 0.0002 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tularemia), Day 7 vs. 0). The average Gene NameGPR84SLC5A6CYB5D1SERPINB2PRMT10 Gene Description ZNF571CCRL2 G protein-coupled receptor 84NR4A3 solute carrier family 5 (sodium-dependentGPR132 cytochrome vitamin b5 transporter), serpin domain member peptidase containing 6 inhibitor, 1 cladeUSP36 B (ovalbumin), member 2 proteinGABPB1 arginine methyltransferase 10 (putative)PDE4D zinc finger protein 571PPIF chemokine (C-C motif) receptor-likeELL2 2 nuclear receptor subfamily 4,PHLDA1 G group protein-coupled A, receptor member 132 3ID3 -0.62 ubiquitin specific peptidase GARANBP2 36 binding protein transcription factor, beta subunitPLAU 1 phosphodiesterase 4D, -5.45 cAMP-specificGAS2L3ZNF184 peptidylprolyl isomerase FZDBF2 pleckstrin elongation homology-like factor, RNA domain, polymerase family <0.0001 A, II, -1.72 member 2MN1 1 0.001 RANOLR1 binding protein 2 inhibitor of DNASMAD7 binding -5.58 3, dominant negative helix-loop-helix plasminogen proteinC15orf48 activator, growth urokinase arrest-specific 2 like 3 -0.76CTH zinc finger protein 184LAMB3 <0.0001 -0.90 -0.70 zinc finger, DBF-type 0.0007 containingADORA2A 2 -5.59SPECC1L-ADORA2A meningioma (disrupted -1.52 in -5.44 -5.53 balanced oxidized translocation) lowNRIP3 1 density SMAD lipoprotein family (lectin-like) -0.69 member receptor 7 chromosome 1SERTAD1 15 -1.01 open <0.0001 reading frame 48 -5.82FAM177A1 0.0007 <0.0001 <0.0001DDIT3 -5.91 -0.66 cystathionase 0.001 (cystathionine laminin, 0.0008 -5.69 gamma-lyase) beta 3 -0.96 -0.61 -1.10 <0.0001 -6.07 -0.59 0.0004 <0.0001 -0.63 SERTA <0.0001 domain -5.67 nuclear containing receptor 0.0004 -5.82 1 interacting -5.98 protein family 3 0.0006 with sequence similarity -5.91 177, member <0.0001 A1 -0.62 -5.87 0.0003 <0.0001 DNA-damage-inducible <0.0001 transcript 3 <0.0001 0.0006 0.0004 -5.96 -0.77 0.0004 <0.0001 <0.0001 0.0004 0.0004 -1.04 -5.92 -1.64 -0.64 <0.0001 0.0004 -0.63 -0.63 -6.24 -6.31 -6.09 <0.0001 -0.66 0.0004 -6.08 -6.10 -1.60 -0.73 <0.0001 -6.16 <0.0001 <0.0001 -0.66 0.0003 0.0002 0.0003 <0.0001 -6.42 -6.13 <0.0001 0.0003 -6.48 0.0003 <0.0001 -0.80 -0.73 0.0003 <0.0001 <0.0001 -6.37 <0.0001 0.0002 0.0003 -1.09 -7.21 0.0002 -0.80 -6.69 <0.0001 -1.09 <0.0001 0.0002 0.0001 -6.82 <0.0001 -8.07 0.0002 <0.0001 0.0002 <0.0001 <0.0001 change was used toannotations were combine obtained probe from Affymetrix sets (HT with HG-U133 Plus the PM same Annotations, Release gene 34,10/24/13). symbol prior to the analysis. Results are sorted by descending t-statistic. Gene Table 79:

Confidential/Proprietary Information -55- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold change was used 2 log FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log 0.960.96 5.15 5.15 <0.00010.83 0.029 <0.0001 0.029 4.82 <0.0001 0.0396 Log Differentially expressed genes (vaccine study comparisons, YF-17D (Yellow Fever), Day 3 vs. 0). The average Gene NameIFI44LSIGLEC1HERC6EPSTI1CMPK2 Gene Description USP18LOC200772 interferon-induced sialic protein acidIRF7 44-like binding Ig-like lectin 1, sialoadhesinIFI44 HECT and RLD domainMX1 containing E3 epithelial ubiquitin stromal protein interaction ligase 1 familyOAS1 (breast) member cytidine 6 monophosphate (UMP-CMP) kinaseLINC00487 uncharacterized 2, LOC200772 mitochondrial ubiquitin specific peptidaseISG15 18XAF1APOBEC3A interferon regulatory factor 7APOBEC3A_B interferon-induced protein 44 0.59RSAD2 myxovirus long (influenza intergenic virus) non-protein resistance coding 2’-5’-oligoadenylate 1, RNA synthetaseLAMP3 interferon-inducible 487 1, protein 40/46kDa p78 (mouse)OAS2 6.49 ISG15 ubiquitin-likeIFIT1 modifier XIAPSCO2 associated factor 1FANCL <0.0001 1.34SASH1 0.0047 1.20 radical 1.71 S-adenosyl methionine domainDDX60 containing 2 lysosomal-associated membrane protein 3 5.89IFI6 5.74 2’-5’-oligoadenylate synthetaseOAS3 7.65 2, 69/71kDa 2.46 interferon-induced protein with tetratricopeptide repeats 1.28 1 <0.0001 Fanconi anemia, complementation <0.0001 group 0.0105 7.77 L <0.0001 SAM and 0.0107 SH3 domain 0.0006 containing 1 6.05 DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 0.75 <0.0001 1.06 interferon, alpha-inducible protein 2’-5’-oligoadenylate 6 synthetaseGene 0.0006 3, Name 100kDa 0.74 1.38 <0.0001HERC6 5.83 0.0105 5.88USP18 0.96 5.53 1.44IFI44L 5.71KLHDC7B 1.39 <0.0001 5.83 <0.0001MX1 Gene 0.0105 Description 5.75 0.0105 RGL1 <0.0001 1.68 <0.0001 1.06 5.05 0.0153 EPSTI1 0.0107 HECT and 0.89 RLD domain containing <0.0001 E3 ubiquitin ubiquitin 0.84 protein specific <0.0001 4.94 ligase peptidase 0.0105 family 18 member 0.99 6 5.40 kelch 0.0107 domain interferon-induced protein containing 44-like 7B 4.98 <0.0001 0.0355 4.96 0.67 5.23 <0.0001 myxovirus (influenza <0.0001 virus) resistance 0.0358 ral 1, guanine 0.98 interferon-inducible nucleotide protein epithelial <0.0001 dissociation 0.02 p78 stromal stimulator-like (mouse) interaction 1 1 (breast) 0.0358 4.81 <0.0001 1.30 <0.0001 0.59 0.0358 4.74 0.0283 0.87 13.93 <0.0001 4.76 1.02 2.18 0.0396 4.66 <0.0001 0.0435 <0.0001 4.67 11.68 <0.0001 <0.0001 0.0435 <0.0001 0.0483 <0.0001 <0.0001 0.0483 <0.0001 1.25 2.32 3.61 11.27 0.79 12.75 2.05 11.82 <0.0001 11.73 <0.0001 11.07 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 to combine probe sets with thefrom same Affymetrix gene (HT symbol HG-U133 prior Plus to PM the Annotations, analysis. Release Results 34,10/24/13). are sorted by descending t-statistic. Gene annotations were obtained Table 80:

Confidential/Proprietary Information -56- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 1.00 10.66 <0.0001 <0.0001 0.981.65 9.451.53 9.31 9.25 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.830.90 8.53 8.48 <0.0001 <0.0001 <0.00010.73 <0.0001 8.080.790.83 7.89 <0.0001 <0.0001 7.78 <0.0001 <0.0001 <0.0001 <0.0001 Gene NameLAMP3SIGLEC1PARP12 XAF1IFI6 Gene Description IFI44OAS2 lysosomal-associated membrane protein sialic 3 acidEIF2AK2 binding Ig-like lectin 1, sialoadhesinPARP9RSAD2 XIAPCMPK2 associated factor 1ISG15 interferon, alpha-inducible protein 6PNPT1 interferon-induced protein 44 2’-5’-oligoadenylate eukaryotic synthetaseHERC5 translation 2, initiation 69/71kDa factor 2-alpha kinaseSPATS2L 2 poly (ADP-ribose) polymerase family,MX2 member 9 radical S-adenosyl methionine domainDDX60 containing 2 cytidine monophosphate (UMP-CMP) kinaseIRF7 2, mitochondrial ISG15 ubiquitin-likeOAS3 modifierLINC00487 spermatogenesis associated,OAS1 serine-rich 2-likeOASLIFIT1 DEAD 2.60 2.23 (Asp-Glu-Ala-Asp) box polypeptideSTAT1 60BST2 interferon long regulatory intergenic factor non-protein 7 coding 2’-5’-oligoadenylate RNA synthetaseDTX3L 10.85 487 10.97 3, 100kDaRNF213 1.02 2’-5’-oligoadenylate synthetaseIFIT3 1, 40/46kDa 2.26 2’-5’-oligoadenylate <0.0001 synthetase-like <0.0001IFI27 1.56 <0.0001 <0.0001 10.03PARP14 interferon-induced protein 1.39 with 2.79 signal tetratricopeptide 1.91 transducer repeats and 1 9.51LGALS3BP activator of transcription 1, 91kDaLOC100507535 10.07 1.83 <0.0001 9.85 9.73SERPING1 2.42 ring 10.58 finger protein <0.0001 213IFI35 <0.0001 10.62 <0.0001 <0.0001 DHX58 interferon-induced protein with tetratricopeptide 10.47 0.84 repeats <0.0001 3LY6E poly interferon, <0.0001 <0.0001 <0.0001 lectin, (ADP-ribose) alpha-inducible galactoside-binding, protein polymerase soluble, 27 family, member 3 14 binding <0.0001 <0.0001 <0.0001 TRIM22 protein <0.0001NEXN serpin 9.27 <0.0001 peptidase <0.0001 inhibitor, clade 2.05 GZBP1 1.83 (C1 <0.0001 inhibitor), member 1 interferon-induced protein 1.78 9.50 35 <0.0001 9.19 1.64 3.05 <0.0001 lymphocyte antigen 6 1.01 complex, 2.11 locus E 9.02 <0.0001 9.16 nexilin 8.60 <0.0001 (F actin binding 1.51 <0.0001 protein) <0.0001 Z-DNA 8.55 binding 8.84 protein 1 1.43 <0.0001 2.33 <0.0001 <0.0001 9.17 <0.0001 <0.0001 <0.0001 8.69 <0.0001 <0.0001 8.36 1.27 <0.0001 <0.0001 2.13 0.68 <0.0001 <0.0001 8.18 <0.0001 8.07 <0.0001 8.33 <0.0001 <0.0001 3.16 0.59 <0.0001 <0.0001 <0.0001 <0.0001 8.35 <0.0001 <0.0001 8.47 <0.0001 1.44 <0.0001 1.40 <0.0001 <0.0001 7.81 7.92 1.48 <0.0001 <0.0001 7.72 <0.0001 0.76 <0.0001 7.72 <0.0001 <0.0001 <0.0001 <0.0001

Conﬁdential/Proprietary Information -57- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.840.990.64 7.55 7.481.06 7.46 <0.00011.39 7.30 <0.0001 <0.00011.39 <0.0001 <0.0001 7.23 <0.0001 0.61 7.23 <0.0001 <0.0001 6.98 <0.0001 <0.0001 <0.0001 <0.0001 <0.00011.23 <0.0001 0.83 6.640.71 6.63 6.52 <0.0001 0.0002 <0.00010.78 0.0002 <0.0001 6.46 0.0002 0.700.75 6.31 <0.0001 0.0002 0.67 6.150.98 <0.0001 6.11 0.0003 0.88 6.02 <0.00010.87 0.0004 5.96 <0.0001 5.96 0.0005 <0.0001 0.0006 <0.0001 0.0006 <0.0001 0.0006 Gene NameSP100CD38UBE2L6 APOL6CXCL10 Gene Description LAP3 GBP1 SP100 nuclear antigenAPOBEC3A CD38APOBEC3A_B molecule SAMD9L apolipoprotein L, 6 FTSJD2 chemokine (C-X-C motif) ligand 10SAMD9SAMD4A guanylate bindingRRM2 protein 1, interferon-inducibleSASH1 sterilePLSCR1 alpha motif domain containing 9-likeSCO2 IFIT5 sterile alpha motif domain sterileRTP4 containing alpha 9 motif domain containing 4ACHMP5 ribonucleotide reductaseDDX58 M2 SAM and SH3 domainDDX60L phospholipid containing scramblase 1 1CCR5TOR1B TMEM255A receptorMARCKS (chemosensory) transporter protein 4SP110 DEAD (Asp-Glu-Ala-Asp) box polypeptideRIN2 DEAD 58 (Asp-Glu-Ala-Asp) box polypeptide 1.24 60-likeTDRD7 0.60 2.35 chemokine (C-CIFIH1 transmembrane motif) protein receptor 255A 5 (gene/pseudogene)KIAA1958 7.25 myristoylated 7.63 alanine-richFBXO6 protein 7.31 kinase 1.77 C substrateTYMPIFITM1 <0.0001 7.17TLR7 Ras <0.0001 and <0.0001 Rab <0.0001 interactor 2 <0.0001 1.17GMPR 0.72 <0.0001 KIAA1958 interferonCCR1 induced with helicase C domainC3AR1 1 <0.0001 F-box 6.95 protein 6.82 6 MS4A4A <0.0001 thymidine phosphorylase 0.78 0.87 0.97 <0.0001 <0.0001 toll-like receptor 7 0.90 0.81 guanosine <0.0001 6.72 0.0001 monophosphate reductase 0.71 0.94 6.78 6.54 chemokine (C-C motif) receptor complement 1 component 3a membrane-spanning receptor 6.47 4-domains, 6.70 1 subfamily 1.15 A, 6.46 member 6.50 4A <0.0001 <0.0001 0.0001 <0.0001 0.0001 0.0002 6.40 <0.0001 <0.0001 <0.0001 <0.0001 0.0002 0.0001 0.0002 0.0002 1.28 <0.0001 0.0003 6.45 0.95 <0.0001 6.15 0.79 0.0002 1.29 6.16 <0.0001 5.85 0.0004 0.67 0.90 1.05 <0.0001 5.95 1.13 <0.0001 0.0004 6.01 0.0008 5.88 5.92 <0.0001 <0.0001 0.0006 0.0006 <0.0001 <0.0001 0.0007 0.0007

Confidential/Proprietary Information -58- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.61 5.660.640.86 5.56 <0.0001 5.51 0.0011 0.670.88 <0.0001 5.32 0.0014 <0.00010.65 5.32 0.0015 0.76 5.27 <0.00010.95 0.0023 <0.00010.67 5.22 0.0023 0.84 5.10 <0.0001 5.02 0.0026 4.98 <0.0001 0.0028 <0.00010.61 0.0037 <0.0001 0.0043 <0.00010.69 4.78 0.0047 0.690.76 4.73 4.73 <0.0001 4.69 0.0071 0.64 <0.0001 0.0078 <0.00010.85 4.62 0.0078 <0.0001 0.0085 4.52 0.00010.66 0.0097 0.0001 4.39 0.0121 0.0002 0.0154 Gene NamePI4K2B C1QALGALS9MT2A MYOF Gene Description FAM46ACCL2VRK2 complement componentFCGR1B lectin, 1, galactoside-binding, q soluble, subcomponent, 9 A chainIFIT2IFI16 myoferlin KMO family with sequence similarity 46, memberPLAC8 A chemokineIFITM3 (C-C motif) ligand 2CECR1 FCGR1C TNFSF10 interferon-induced protein with tetratricopeptide repeats 2FANCLRAD51AP1 kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)PSME2 PGAP1FAM225A 0.71 tumor necrosisFAM225B factor (ligand) superfamily, member 10IFITM2 RAD51 associated Fanconi anemia, protein complementation 1 groupLOC200772 5.63 LNAPA 0.59SLC31A2 post-GPI attachment to 0.64 proteinsCDKN1C 1 <0.0001CTSL1 0.0012 1.27 5.61MAFB uncharacterized LOC200772 5.46 1.03ANKRD22 5.28CX3CR1 <0.0001 N-ethylmaleimide-sensitive factorHPSE attachment 5.24 protein, alpha 0.0012 0.95 <0.0001 cyclin-dependentTCF7L2 kinase inhibitor 1C 0.0017 (p57, Kip2)WARS <0.0001 cathepsin L1 0.0025 CLEC4F 1.13 5.35 <0.0001 ankyrin repeat v-maf domain musculoaponeuroticGBP3 22 fibrosarcoma 0.0027 oncogene homolog B (avian) chemokineMS4A7 (C-X3-C motif) receptor 4.86 1SLC27A3 <0.0001 heparanase 0.0022 transcription factor 7-like 0.77 2 (T-cell specific, HMG-box) tryptophanyl-tRNA synthetase <0.0001 C-type lectin domain family 0.0061 4, member F 4.81 guanylate binding protein 0.61 3 membrane-spanning 0.64 4-domains, solute subfamily A, carrier member family 27 7 (fatty 0.70 acid transporter), member 3 0.67 <0.0001 4.63 4.78 0.0067 4.51 0.61 4.74 0.64 0.0001 <0.0001 0.007 0.0097 0.0001 4.57 <0.0001 4.68 0.0122 0.0076 0.63 0.0001 <0.0001 0.0108 0.74 4.36 0.0087 0.73 0.69 1.11 4.40 0.66 4.20 0.0002 4.19 4.44 0.0165 0.59 0.0002 4.26 0.0003 0.0151 0.0003 0.0002 4.30 0.0219 0.60 0.0219 0.0139 0.0003 0.0197 0.0002 4.20 0.0181 0.0003 0.0219

Conﬁdential/Proprietary Information -59- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold change was used 2 log FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log 0.690.690.95 4.190.63 4.190.59 4.130.62 4.11 0.0003 4.07 0.00030.61 0.0219 4.02 0.0004 0.0219 0.0004 0.0248 3.91 0.0004 0.0259 0.0005-0.60 0.0276 -0.59 0.0306 0.0007 -4.29-0.60 0.0361 -4.58 0.0003 -7.05 0.0001 0.0184 0.0107 <0.0001 <0.0001 Log 0.990.98 6.521.27 5.681.13 <0.00011.13 5.33 0.002 1.13 5.25 <0.00011.13 5.25 0.0082 1.13 5.25 <0.00011.13 5.25 0.0115 <0.00011.13 5.25 0.0115 <0.00011.23 5.25 0.0115 <0.00011.23 5.25 0.0115 <0.0001 5.24 0.0115 <0.00010.66 5.24 0.0115 <0.00011.61 0.0115 <0.00011.19 5.16 0.0115 <0.0001 5.13 0.0115 <0.0001 5.09 0.0115 <0.0001 0.012 <0.0001 0.0125 <0.0001 0.0127 Differentially expressed genes (vaccine study comparisons, YF-17D (Yellow Fever), Day 7 vs. 0). The average Gene NameOTTHUMG00000003319 RP4-781L3.1 DUSP6 TNFSF13B PSMB9 Gene Description IL15 TMEM140NAGK NLRP3XKKITNGLY1 transmembrane protein 140LOC439911 RPS23ITGAE NLR family, pyrin domain containing 3 X-linked Kx blood group (McLeod v-kit syndrome) Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog ribosomal protein S23Gene NameIGHG2 IGKCIGLL3P IGKIGKV1-17 Gene Description AC127391.1 -0.62AC128677.4 IGKV1OR10-1 immunoglobulinIGKV1OR-2 kappa -4.18 constantIGKV1OR2-118 0.68OTTHUMG00000155081 0.75 immunoglobulin 0.66 kappa locusOTTHUMG00000155090 0.0003AC016745.2 3.97 0.0224 3.88OTTHUMG00000153338 3.84IGHMIGHV4-31 0.0006 0.0007IGLV1-36 0.0008 0.0325 IGLJ2 0.0381 0.0405 -0.68 immunoglobulin heavy constant mu -5.75 <0.0001 0.0009 0.80 5.88 0.96 <0.0001 5.57 0.0056 <0.0001 0.01 0.61 5.17 <0.0001 0.012 to combine probe sets with thefrom same Affymetrix gene (HT symbol HG-U133 prior Plus to PM the Annotations, analysis. Release Results 34,10/24/13). are sorted by descending t-statistic. Gene annotations were obtained Table 81:

Conﬁdential/Proprietary Information -60- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log 0.80 4.941.211.211.12 4.80 <0.00011.13 4.80 0.0153 1.13 4.780.66 4.77 <0.00010.67 4.77 0.0166 <0.00010.61 4.71 0.0166 <0.00011.24 4.61 0.0168 <0.0001 4.52 0.017 <0.00010.61 4.51 0.017 <0.0001 0.0184 0.00011.07 4.45 0.0001 0.0217 0.00010.88 0.0242 4.200.81 0.0245 0.00020.81 4.18-0.72 0.0265 4.05 0.0003 4.05 0.0351 -4.04 0.0003 0.0004-1.26 0.0359 0.0004-0.72 0.0416 0.0004-1.30 0.0416 -4.31 0.0416 -4.80-0.78 -4.82 0.0002-0.73 <0.0001 -5.06 0.031 -0.63 0.0166 <0.0001-1.04 0.0166 -5.22 <0.0001 -5.32 0.0129 -5.36 <0.0001-1.53 0.0115 <0.0001-1.39 0.0115 <0.0001 0.0115 -7.68 -7.81 <0.0001 0.0003 <0.0001 0.0003 Gene NameIGLJ3IGHV3-23 IGLV1-44IGHDIGKV1-37 Gene Description IGKV1D-37 IGLV1-50 immunoglobulin lambdaBLOC1S5-TXNDC5 joining 3 immunoglobulin lambdaTXNDC5 variable 1-44IGHG3 immunoglobulinIGLV3-19 heavy constant deltaIGHA2 IGLV3-10 TNFRSF17PRDX4 MZB1IGLV2-14 IGJIGLV3-1 tumor necrosis factor receptor superfamily,IGKV2-28 member 17IGKV2D-28 SGK1 marginal zoneEGR2 B and B1 cell-speciﬁc proteinGABARAPL3CXCL2 immunoglobulin J polypeptide,IL1B linker protein 0.71 for immunoglobulin alpha 1.01 andPFKFB3 mu polypeptidesIL8 0.59 GABA(A) 0.77 receptors 4.87LOC284454 associated protein 4.95 like 3, pseudogene early growthCD83 response 2EGR3 4.84 4.19 chemokine (C-X-C motif) ligandOSM <0.0001 2 1.42 <0.0001 0.0165 NFIL3 interleukin 0.0151 1, beta G0S2 uncharacterized LOC284454 <0.0001 0.0003 4.47RGS1 0.0166 interleukin 0.0359 8 PTGS2NR4A3 early growthBRE-AS1 0.0001 response 3NR4A2 oncostatin 1.18 M 0.0256 -0.62 4.38 regulator of G-protein signaling prostaglandin-endoperoxide 1 synthase 2 (prostaglandin G/H -4.22 synthase nuclear and receptor cyclooxygenase) subfamily 4, group A, member 3 0.0002 -1.15 0.0292 0.0003 0.0344 -5.89 -0.72 <0.0001 -0.90 0.0056 -4.22 -4.17 -0.75 0.0003 -4.97 0.0003 0.0344 0.0359 -0.64 <0.0001 -0.85 0.0147 -6.74 -0.80 -5.21 -5.42 <0.0001 0.002 <0.0001 0.0115 <0.0001 0.0115

Confidential/Proprietary Information -61- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold change was used to 2 log FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log Log 0.60 5.76 <0.0001 0.0011 -0.66-1.16-0.60 -3.22-0.74 -3.27 -3.35-0.73 0.0034 -3.46-0.72 0.0029 0.0373 0.0024 -3.69 0.0343 0.0018 -3.90 0.0298 -0.59 0.025 -1.28 0.001-0.65 0.0006 -4.26 0.0173 -4.27 0.0123 -0.62 -4.42 0.0002-0.67 0.0002 -4.71 0.007 0.0001 0.007 -4.88 0.0057 -0.60 <0.0001 0.0036 <0.0001 -5.05 0.0027 <0.0001 0.0021 Differentially expressed genes (vaccine study comparisons, TIV (Influenza), Day 7 vs. 0). The average Gene Name Gene Description Gene NameOAS1SMCO4KCTD12 IDH1RAB10 Gene Description TNFSF10GAPT 2’-5’-oligoadenylate synthetaseCCR2 1, single-pass 40/46kDa membrane protein with coiled-coilGIMAP4 domains 4SLC25A37PFKFB3 isocitrate dehydrogenase 1 RAB10, (NADP+), member tumor soluble RAS necrosisIL8 oncogene factor family (ligand) superfamily, member 10THBS1 GRB2-binding adaptorBCL2A1 protein, transmembrane chemokine (C-CMXD1 GTPase, motif) IMAP receptor solute family 2 carrier member 4 family 25NR4A2 (mitochondrial iron transporter), member 37OSMCSRNP1NAMPT thrombospondin 1 interleukin 8 RPS27 0.82G0S2 MAX dimerizationSLC2A14 protein 1SLC2A3 7.11 0.96 cysteine-serine-richGPR183 oncostatin nuclear M protein 1TP53INP2 0.70 nicotinamide -0.62 phosphoribosyltransferaseATG2A 7.89 <0.0001 0.64PDE4B 0.0003 5.18 -3.04METRNL 0.62 0.69NXT1 solute 5.30 carrier <0.0001 family 2 (facilitated glucoseBTG3 0.0002 transporter), member tumor 3 0.0052 protein <0.0001 p53GABARAPL3 inducible 4.29 nuclear 5.21 protein 2 0.0018 0.0496 GABARAPL1 <0.0001 autophagy related 2A MAFF 0.0015 phosphodiesterase 4B, cAMP-specific 0.71 meteorin, glial cell 0.67 0.0002 differentiation regulator-like <0.0001 0.0017 0.0069 GABA(A) receptors associated protein 3.94 like 3, GABA(A) pseudogene receptor-associated BTG 3.86 protein family, member like 3 1 0.0005 -0.69 v-maf musculoaponeurotic fibrosarcoma 0.0006 oncogene homolog F 0.0115 (avian) 0.0131 -0.62 -0.92 -4.68 -0.71 -3.98 -4.22 -3.60 <0.0001 0.0037 -0.63 0.0005 0.0002 0.0013 -0.75 0.011 0.0075 -1.02 -4.85 0.0202 -0.59 -5.08 -0.82 -5.16 -5.05 <0.0001 0.0029 -0.64 -5.00 <0.0001 <0.0001 0.002 <0.0001 0.0018 -5.11 0.0021 <0.0001 0.0022 <0.0001 -0.62 0.0019 -5.07 <0.0001 0.002 combine probe sets with thefrom same Affymetrix gene (HT symbol HG-U133 Plus prior PM to Annotations, the Release analysis. 34,10/24/13). Results are sorted by descending t-statistic. Gene annotations were obtained Table 82:

Confidential/Proprietary Information -62- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold change was used to 2 log FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log -0.59 -6.23 <0.0001 0.0006 Log 0.59 4.95 <0.0001 0.0029 0.62 4.11 0.0004-0.66 0.0077 -0.68 -3.05 -3.07-0.76-0.63 0.0052 0.005 -3.25 0.0406 -3.25 0.0394 0.0032 0.0032 0.03 0.0299 -0.62 -3.96 0.0005 0.0094 Differentially expressed genes (vaccine study comparisons, LAIV (Influenza), Day 3 vs. 0). The average Gene NameZNF331JOSD1 JMYZBTB21CREM Gene Description zinc finger protein 331 zinc junction finger mediating and and BTB regulatory domain protein, containing p53 21 cofactor cAMP responsive elementGene modulator NameLOC100506776KCTD12 DENND2DOAS1 uncharacterizedSGK223 LOC100506776 Gene Description MS4A7IDH1GIMAP4 DENN/MADD domain containing 2DGIMAP6 RAB10 2’-5’-oligoadenylate synthetaseSMCO4 homolog 1, of 40/46kDa -0.63 rat pragma of Rnd2COPB2 membrane-spanning 4-domains, subfamily A,GAPT member 7 -6.35CCR2 isocitrate GTPase, IMAP dehydrogenase 1 family member (NADP+), 4 soluble -0.80SLC25A37SGK1 RAB10, member <0.0001 RASTHBS1 oncogene -1.14 family single-pass -0.79 -6.84 membrane 0.0005 protein with coiled-coilCLC domains 4 coatomer protein complex, subunitCXCL2 beta 2 (beta -5.28 prime) -7.48 GRB2-binding adaptorPROK2 protein, transmembrane <0.0001 solute carrier family chemokine 25 (C-CBTG1 (mitochondrial motif) 0.0003 iron receptor transporter), 2 member 37RAB20 <0.0001 <0.0001S100P 0.0015 thrombospondin 0.0002 0.69 1 PLAUR 0.63CXCL1 Charcot-Leyden crystal chemokine galectin (C-X-C motif) ligandACSL1 5.06 2 prokineticin 0.60 2 0.80B3GNT5 4.39C5AR1 RAB20, member RAS 4.93 oncogene 4.91 family <0.0001 S100 0.68 0.67 calcium binding protein 0.0026 -0.72 P plasminogen activator, urokinase 0.0002 receptor 0.60 chemokine (C-X-C 0.59 motif) 0.0054 ligand <0.0001 4.28 1 <0.0001 4.02 (melanoma acyl-CoA growth synthetase -2.96 stimulating long-chain activity, UDP-GlcNAc:betaGal alpha) 0.0029 family 0.003 beta-1,3-N-acetylglucosaminyltransferase member 5 0.76 1 4.51 0.69 3.98 0.65 0.0002 0.0004 0.0066 4.25 4.09 0.0062 0.0001 0.0086 0.0469 3.83 0.0005 0.0047 -0.77 0.0092 0.0002 0.0004 0.75 -3.65 0.0065 0.0007 0.0079 0.0117 -0.59 3.26 0.0012 -1.62 -0.59 -3.93 0.0159 0.0031 -0.74 -0.60 -3.12 0.0294 -3.22 -0.88 0.0006 -3.29 0.01 -3.58 -1.18 -3.75 0.0044 0.0035 0.0361 0.0315 0.0029 -3.38 0.0014 0.0284 0.0009 0.0176 0.0133 0.0023 0.0247 combine probe sets with thefrom same Affymetrix gene (HT symbol HG-U133 Plus prior PM to Annotations, the Release analysis. 34,10/24/13). Results are sorted by descending t-statistic. Gene annotations were obtained Table 83:

Confidential/Proprietary Information -63- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.95-0.60 -3.97-0.59 -4.04-0.75 0.0005 -4.14 0.0093 0.0004 -4.20-0.60 0.0083 -0.84 0.0003-0.59 0.0003 -4.29 0.0073 -0.89 -4.34 0.007 -0.59 -4.34 0.0002 -4.37 0.0002 -4.40 0.0062 -1.04 0.0002 0.0058 -0.61 0.0002 0.0058 0.0002 -4.50 0.0055 -1.47 -4.54 0.0053 0.0001 -4.68 0.0001 0.0047 -0.70 0.0046 -0.70 <0.0001-0.74 0.0038 -4.79 -4.79-0.64 -4.85 <0.0001-1.19 0.0033 <0.0001 -5.02-0.91 0.0033 <0.0001-0.84 0.0032 -5.08-0.64 <0.0001 -5.10 0.0027 -5.13 <0.0001 -5.14 0.0025 <0.0001 0.0025 <0.0001 0.0025 <0.0001 0.0025 Gene NameAREGB TREM1C1orf132 TMCC3WHAMM Gene Description CD83 MXD1EGR2 triggering receptor expressed onNXT1 myeloid cells 1BCL2A1 transmembrane and coiled-coil domainDBF4 family 3OSMNRBF2 MAX dimerizationFAM46C protein 1 early growthBTG3 response 2PFKFB3 THBDSAMSN1IL8 oncostatin M familyEGR3 with sequence similarity 46, memberMAFF C BTGPHACTR1 family, member 3OTTHUMG00000176282 -0.78 thrombomodulin SAMRP11-469M7.1 domain, SH3 domain and nuclear localizationATG2A signals 1 -0.59 -4.03TAF13 interleukin early 8 growthMAPK6 response 3 phosphatase and -4.13 v-maf actin musculoaponeuroticTP53INP2 regulator fibrosarcoma 1 oncogene homolog F 0.0004 (avian)BRE-AS1 NFIL3 0.0084 0.0003SLC2A14 autophagy related 2A 0.0074 FAM53C TAF13 RNA polymeraseZNF331 II, box TATA binding tumor protein protein (TBP)-associated p53 factor,RGS1 18kDa inducible nuclear -0.85 protein 2GABARAPL1 -0.61 -0.62PTGS2 -0.72 -0.95 -4.23GABARAPL3 -0.60SLC2A3 -4.66 -4.44 -4.24 -4.70SPTY2D1 zinc finger protein GABA(A) 0.0003 331 receptor-associated -4.97 protein like 1 regulator 0.0067 of <0.0001 G-protein 0.0001 signaling 1 0.0002 GABA(A) receptors 0.0039 <0.0001 associated protein like prostaglandin-endoperoxide 0.0051 3, synthase pseudogene 2 0.0037 0.0065 <0.0001 (prostaglandin G/H synthase and cyclooxygenase) 0.0028 -0.63 solute carrier family SPT2, 2 Suppressor (facilitated glucose of transporter), Ty, domain -1.48 member containing 3 1 (S. cerevisiae) -4.50 -0.74 -5.35 -0.74 -4.78 0.0001 -0.60 0.0047 <0.0001 -4.69 0.0022 <0.0001 -5.04 0.0034 <0.0001 -0.80 0.0038 -0.86 <0.0001 0.0027 -0.64 -5.35 -0.62 -5.36 -5.26 -5.39 <0.0001 -0.73 0.0022 <0.0001 0.0022 <0.0001 -1.18 <0.0001 0.0023 -5.18 0.0022 -5.17 <0.0001 0.0025 <0.0001 0.0025

Confidential/Proprietary Information -64- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. fold change was used to 2 log FC t-Statistic P FDR FC t-Statistic P FDR FC t-Statistic P FDR 2 2 2 Log -1.43 -5.48-0.70 <0.0001 -5.96 0.0021 -0.66 <0.0001 0.0014 -1.25 -6.33 -6.98 <0.0001 0.001 <0.0001 0.0006 Log -0.86 -4.95-1.05 <0.0001 -6.13 0.0462 <0.0001 0.0017 Log 1.111.11 4.15 4.15 0.0001 0.0001 0.0132 0.0132 fold change was used to combine probe sets with the same gene symbol prior to the analysis. Results are sorted by descending 2 log Differentially expressed genes (vaccine study comparisons, LAIV (Influenza), Day 7 vs. 0). The average Differentially expressed genes (vaccine study comparisons, (Tularemia) DVC-LVS/USAMRIID-LVS Day 2 vs. YF-17D (Yellow Fever) Day 3). Gene NameJMYG0S2 NR4A3PDE4BGPR183 Gene Description CSRNP1ZNF267HSPA13 junction mediating and regulatoryNAMPT protein, p53 cofactor nuclear receptor subfamily 4,GTF2B group A, phosphodiesterase member 4B, 3 cAMP-specificZBTB21 cysteine-serine-richNR4A2 nuclear protein 1CREM zinc finger protein 267 heat shock protein 70kDa family, member 13 nicotinamide phosphoribosyltransferase zinc finger and BTB domain containing 21 cAMP responsive elementGene modulator NameIL1A -0.59SIGLEC1IFI44L -5.44LAMB3 -0.69 Gene Description <0.0001 -5.56 0.0022 -0.94 sialic acid binding interleukin Ig-like 1, lectin alpha 1, sialoadhesin -0.79 interferon-induced <0.0001 protein -5.95 -0.62 44-like laminin, 0.0021 beta 3 Gene Name -1.25 -5.97LOC100507018 -6.28 <0.0001RPS23 0.0014 -0.90LOC100506328 -6.30 <0.0001N4BP2L2-IT2 -0.73 <0.0001 0.0014 uncharacterizedTAPT1-AS1 LOC100507018 0.001 Gene -6.93 Description METTL3 <0.0001 -0.85 -6.11 0.001 uncharacterizedCTB-167B5.2 LOC100506328OTTHUMG00000179513 <0.0001 ribosomal N4BPL2 -7.61 protein intronic S23 transcriptST20 2 0.0006 (non-protein coding) <0.0001 TAPT1 antisense 0.0013 RNA 1 (head to head) <0.0001 methyltransferase like 3 -1.30 0.0006 -5.20 suppressor of tumorigenicity 20 -1.83 <0.0001 0.0462 -5.46 <0.0001 0.68 0.0462 0.70 0.69 4.37 5.42 0.59 4.54 <0.0001 <0.0001 0.0068 4.27 0.0004 0.71 <0.0001 0.004 4.78 <0.0001 0.63 0.0086 0.73 4.20 <0.0001 0.0027 4.15 <0.0001 0.0104 0.0001 0.0132 combine probe sets with thefrom same Affymetrix gene (HT symbol HG-U133 Plus prior PM to Annotations, the Release analysis. 34,10/24/13). Results are sorted by descending t-statistic. Gene annotations were obtained Table 84: Table 85: The average t-statistic. Gene annotations were obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Conﬁdential/Proprietary Information -65- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.64-0.64 -3.61 -3.61 0.0008 0.0008 0.0467 0.0467 -0.90-0.90 -4.02 -4.02 0.0002 0.0002 0.016 0.016 -0.60 -4.18-1.34-0.64 <0.0001 0.011 -4.23-1.43 -4.38 0.0001 -4.43 <0.0001 0.012 0.0068 <0.0001 0.007 mic domain, (semaphorin) 4A Gene NameJMYGMPRFAM225A FAM225B TYMP Gene Description NR4A3CCL4SAMD9L junction mediating guanosine and monophosphate regulatory reductaseUSP36 protein, p53 cofactorCDKN1ANAPA thymidine phosphorylaseCCL20 nuclear receptor subfamily 4,PIWIL4 group A, member 3 chemokine sterilePPP1R15A (C-C alpha motif) motif ligand domain 4 containing 9-likeOTTHUMG00000184015 ubiquitin speciﬁc peptidase cyclin-dependentRP6-99M1.2 36 kinase inhibitor 1A (p21, Cip1)CCRN4L N-ethylmaleimide-sensitive factorAVPI1 attachment protein, alpha chemokine (C-C motif)FNIP2 ligand protein 20 piwi-like phosphatase RNA-mediated 1, gene regulatory silencing subunitMS4A4A 4 15ASLC5A6 -0.76C1QA CCR4SEMA4A carbon catabolite repression 4-like -3.52 (S. cerevisiae) arginine vasopressin-inducedRTP4 1 folliculin interacting -0.59 membrane-spanningADORA2B protein 4-domains, 2 subfamily A, member 0.0008 4ATNF solute carrier -1.50 family 5 (sodium-dependentSPHK1 0.0494 vitamin transporter), -3.59 member 6 complement sema componentRASGEF1B domain, 1, -0.73 immunoglobulin q domain subcomponent, (Ig), A transmembrane -3.68 chain domainPTX3 (TM) and short -1.09 cytoplas- -0.87HAVCR2 0.0007 adenosine -3.89 A2b receptor receptorGBP1 (chemosensory) transporter protein 0.0433 -0.71 4 -3.78 0.0005C15orf48 -3.89 -1.33DDIT3 0.0388 RasGEF domain tumor sphingosine family, necrosis member 0.0003 kinase factor -1.01 1B 1 -3.65MN1 -0.59 -0.63 -0.61 0.0005 0.0225 -3.70NLRP3 0.0003 -0.60 hepatitis pentraxin 0.0367 EMP1 -3.99 A 3, virus long 0.0237 cellular -3.85 -4.12 receptor -2.03 2 -4.06 0.0006FAM46A -1.01 -3.99 guanylate chromosome 0.0006 bindingSERTAD1 15 protein 0.0405 open 1, reading interferon-inducible frame 48 0.0002 0.039 -3.96 -4.11 0.0003 0.0001 DNA-damage-inducible transcript 0.0002 3 0.0175 0.0002 0.0251 0.0128 meningioma 0.0152 (disrupted NLR -0.67 in family, pyrin balanced domain 0.0197 translocation) containing 1 0.0002 3 0.0002 epithelial -0.78 membrane family protein with 1 sequence 0.0197 SERTA similarity 0.02 domain 46, containing -4.15 member 1 A -0.75 -4.07 -0.75 0.0001 -4.09 0.0132 0.0002 -4.21 0.0148 0.0001 -1.21 0.0141 0.0001 -0.73 -0.90 0.0132 -4.39 -4.21 -0.61 -4.47 -1.21 -2.21 <0.0001 -4.45 <0.0001 0.0071 -4.61 -4.50 -0.92 0.0101 <0.0001 0.0075 -0.61 -1.18 <0.0001 -4.59 <0.0001 <0.0001 0.0052 -4.68 0.004 0.0074 -4.63 -0.88 <0.0001 -0.99 0.0039 <0.0001 <0.0001 -4.67 0.0055 0.0037 -4.68 <0.0001 0.0031 <0.0001 0.004

Conﬁdential/Proprietary Information -66- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.68 -4.74-0.76 <0.0001-0.96 0.0028 -4.82 -4.86-0.80 <0.0001-0.80 0.0019 <0.0001 0.0017 -4.99 -4.99 <0.0001 0.0011 <0.0001 0.0011 -1.20-0.94 -5.30 -5.31 <0.0001 0.0008 <0.0001 0.0008 Gene NameSIK3DCUN1D3LRRC32ZBP1C10orf137 Gene Description CUL1DMXL2 DCN1, defective in cullinF3 SIK neddylation family 1, kinase domain 3 containing 3PHLDA1 leucine rich repeat containing 32OLR1 chromosome 10 open Z-DNAADORA2A reading binding frame protein 137 1SPECC1L-ADORA2A cullinCNP 1 Dmx-like 2 PLSCR1SAMD4A pleckstrin homology-like domain, family A, coagulation member factorVSIG10L 1 III (thromboplastin, tissue factor) oxidized lowIFI35 density lipoprotein (lectin-like) receptor 1NRIP3OAS1 -0.60CTSL1 phospholipid 2’,3’-cyclic scramblase 1 nucleotide 3’ phosphodiesterase sterileIL1A alpha motif domain containing -4.75 4A V-setNEXN and immunoglobulin domain containing 10 likeSAMD9GADD45B interferon-induced protein 35 nuclear <0.0001 receptor interactingGAS2L3 protein 3 0.0022 2’-5’-oligoadenylate synthetaseCYB5D1 1, 40/46kDa cathepsin L1 MASTL -0.60PHLDA2 interleukin -0.62 1, alpha -1.36 nexilin (FIL1RN actin binding sterile protein) alpha growth arrest motif and domain -4.81 -1.09CCL2 DNA-damage-inducible, containing beta 9 -1.56 -4.76DDX60L -4.93 growth arrest-speciﬁc 2 like 3PGAP1 cytochrome b5 -4.87 domain -0.60 containing -4.94 1 <0.0001IFIH1 microtubule associated <0.0001 0.0023 serine/threonine kinase-likeRIN2 pleckstrin <0.0001 homology-like domain, 0.0022 family A, -4.80 0.0015 memberTMEM255A 2 <0.0001 <0.0001 interleukin -0.59 1CCRL2 -0.59 receptor 0.0018 antagonist 0.0013 chemokineC3AR1 (C-C DEAD motif) (Asp-Glu-Ala-Asp) ligand box polypeptide 2 <0.0001 60-likeSTAT1 -0.61 -5.16 post-GPI -5.00 attachment 0.0024 to proteinsCXCL10 1 interferon transmembrane induced protein with 255A -5.14 helicase -0.83 C domain 1 Ras <0.0001 and <0.0001 Rab -1.50 interactor 2 0.0007 0.0011 chemokine (C-C -1.38 motif) -5.01 receptor-like 2 <0.0001 complement component 3a -5.28 receptor -1.10 1 0.0016 -0.70 signal transducer and -5.17 activator chemokine of (C-X-C transcription motif) 1, ligand 91kDa 10 <0.0001 -5.17 0.0011 -5.35 <0.0001 -1.06 -1.00 -0.65 0.0009 <0.0001 -1.29 0.0009 -5.32 -5.45 <0.0001 <0.0001 -5.46 0.0011 -0.82 0.0004 -5.32 -0.78 -0.88 <0.0001 <0.0001 -5.38 <0.0001 0.0008 0.0006 -5.36 <0.0001 0.0005 -5.57 0.0006 -0.65 <0.0001 -0.97 0.0004 -1.34 <0.0001 <0.0001 -5.46 -0.86 0.0004 -0.83 0.0006 -5.68 -5.47 -5.60 -5.79 -1.22 -1.39 <0.0001 0.0003 -1.25 <0.0001 <0.0001 -5.74 0.0005 -1.03 -5.76 <0.0001 0.0003 <0.0001 0.0008 -5.78 0.0002 -2.11 -5.71 <0.0001 <0.0001 -5.85 0.0006 0.0001 <0.0001 0.0002 <0.0001 0.0001 <0.0001 0.0003

Confidential/Proprietary Information -67- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.94 -6.08 <0.0001 <0.0001 -1.32 -6.34-0.83 <0.0001 -6.53 <0.0001 <0.0001 <0.0001 Gene NameGPR84LGALS3BPLCP2LY6EFOSL1 Gene Description CCR1DDX60 lectin, galactoside-binding, G soluble, protein-coupled 3 receptor binding 84PARP14 proteinSERPING1 lymphocyteIFIT1 cytosolic protein 2 (SH2 domain lymphocyteIFIT3 containing antigen leukocyte 6 protein FOS-like complex, of antigen locus 76kDa) 1 ELAMB3 chemokine (C-CZCCHC2 motif) receptor DEAD 1 (Asp-Glu-Ala-Asp) box polypeptidePARP9 poly 60 (ADP-ribose) serpin polymerase peptidase family, inhibitor, member clade 14 GKIAA1958 (C1 inhibitor), member -0.80 1MAFBMARCKS interferon-induced protein with tetratricopeptide repeats -6.04 1KLHDC7B interferon-induced protein with laminin, tetratricopeptide beta repeats 3 zinc 3OAS2 finger, CCHC domain containing 2XAF1 poly (ADP-ribose) KIAA1958 polymerase -1.07 <0.0001 family,OAS3 member 9 <0.0001 IRF7 v-maf myristoylated alanine-rich musculoaponeuroticISG15 fibrosarcoma protein -6.03 oncogene kinase homolog C kelch B substrate domain (avian) containingSPATS2L 7BCMPK2 2’-5’-oligoadenylate synthetaseRSAD2 2, <0.0001 69/71kDa -1.79 XIAPLDLR 0.0002 associated -1.40 factor 1 2’-5’-oligoadenylate synthetaseIFI27 3, 100kDa -1.42 -0.68 -6.24LINC00487 -1.40 interferon -2.57 regulatory factor -5.89 7 spermatogenesis ISG15 associated, ubiquitin-likeIFI6 modifier serine-rich -2.00 2-like -6.07 -6.17EPSTI1 cytidine -6.17 monophosphate -1.38 -6.27 (UMP-CMP) -1.40 <0.0001 kinaseOASL 2, mitochondrial radical S-adenosyl <0.0001 -6.32 0.0002 methionine domainIFI44 containing 2 <0.0001 <0.0001 -6.55 low <0.0001EIF2AK2 density -6.12 long lipoprotein intergenic receptor <0.0001 <0.0001 non-protein <0.0001 <0.0001 coding RNAMX1 interferon, 487 alpha-inducible 0.0001 -1.08 protein <0.0001 27 <0.0001SIGLEC1 -1.29 <0.0001 -0.68 <0.0001RGL1 <0.0001 epithelial interferon, stromal alpha-inducible -6.52 interaction <0.0001 protein 1 6 <0.0001 LAMP3 (breast) -6.59 2’-5’-oligoadenylate -6.40 synthetase-likeIFI44L eukaryotic interferon-induced translation protein initiation 44 factor 2-alpha <0.0001 kinase 2 <0.0001 -1.21 <0.0001 sialic <0.0001 acid binding myxovirus Ig-like -2.08 (influenza lectin <0.0001 virus) <0.0001 1, resistance sialoadhesin 1, interferon-inducible protein p78 (mouse) ral -7.00 -0.64 guanine -1.54 nucleotide dissociation lysosomal-associated stimulator-like membrane -0.79 1 -7.78 protein 3 interferon-induced protein 44-like -2.48 -6.82 -7.49 <0.0001 -7.76 <0.0001 <0.0001 -1.98 -1.47 <0.0001 -7.79 <0.0001 -1.40 <0.0001 -1.91 <0.0001 <0.0001 <0.0001 -1.68 -8.97 -7.20 <0.0001 <0.0001 -7.52 -7.73 <0.0001 -8.03 -3.19 -1.09 -0.87 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 -1.79 <0.0001 -8.02 <0.0001 -1.78 -8.81 -7.94 <0.0001 <0.0001 <0.0001 -1.69 -8.25 -2.46 -1.48 -8.13 <0.0001 <0.0001 <0.0001 -8.28 <0.0001 <0.0001 <0.0001 -9.20 -2.19 <0.0001 -9.59 -2.12 <0.0001 <0.0001 <0.0001 <0.0001 -8.66 <0.0001 <0.0001 -9.63 <0.0001 <0.0001 <0.0001 -3.30 <0.0001 <0.0001 <0.0001 <0.0001 -9.72 <0.0001 <0.0001

Confidential/Proprietary Information -68- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR FC t-Statistic P FDR FC t-Statistic P FDR 2 2 2 Log Log -0.88 -4.69 <0.0001 0.0174 Log -0.93 -3.79 0.0005 0.0464 fold change was used to combine probe sets with the same gene symbol prior to the analysis. Results are sorted by descending 2 fold change was used to combine probe sets with the same gene symbol prior to the analysis. Results are sorted by descending log 2 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tularemia) Day 2 vs. TIV (Influenza) Day 3). The Differentially expressed genes (vaccine study comparisons, (Tularemia) DVC-LVS/USAMRIID-LVS Day 7 vs. YF-17D (Yellow Fever) Day 7). log Gene NameUSP18HERC6 Gene Description ubiquitin specific peptidase 18 HECT and RLD domainGene containing Name E3 ubiquitin protein ligase familyMETTL3 member 6ERV3-2GBP1P1TMEM52BCYP1B1 Gene Description CCRL2 -1.20OLR1 methyltransferase like 3IL1A endogenous retrovirus group -11.43 3, memberC11orf96 guanylate 2 binding protein transmembrane 1, protein interferon-inducible 52B pseudogeneCYB5D1 1PHLDA1 cytochrome P450, <0.0001 family 1, subfamily B,FAM177A1 polypeptide <0.0001 1 chemokine (C-C motif) receptor-likeCTH 2 oxidized lowNRIP3 density lipoprotein (lectin-like) receptor chromosome 1 11 interleukin open 1, reading alpha frame 96 cytochrome b5 domain containing 1 pleckstrin homology-like family domain, with family sequence A, similarity member 177, 1 member -2.24 A1 0.82 cystathionase (cystathionine -10.20 gamma-lyase) nuclear receptor interactingGene protein Name 3PTPRE 4.12PTGS2 <0.0001 <0.0001 IGKC -0.79 0.67IGLV3-1 0.0001CXCL3 Gene Description -4.19 0.0415 CCL20 -1.35 4.25SMAD7 protein 0.59 tyrosine phosphatase, receptorZNF571 type, E prostaglandin-endoperoxide synthase -0.59 -4.61 2 <0.0001 (prostaglandinSERPINB2 G/H -0.71 synthase and 0.0001 0.0411 -0.91 cyclooxygenase) immunoglobulin 4.28DDIT3 kappa constant 0.0414 -4.19 -0.67 1.14 -0.76 chemokine -4.48 (C-X-C <0.0001 motif) -5.53 ligand 3 0.0225 chemokine (C-C motif) ligand <0.0001 20 -0.64 SMAD family -4.91 member -5.56 3.92 7 0.0001 0.0308 zinc serpin finger <0.0001 peptidase protein inhibitor, 571 clade -0.65 <0.0001 B 0.046 (ovalbumin), 0.0303 member 2 -5.05 0.0087 <0.0001 DNA-damage-inducible <0.0001 transcript 0.0002 3 -5.59 0.0174 -0.95 0.0066 0.0316 <0.0001 0.0134 -5.71 <0.0001 0.0066 0.65 <0.0001 0.0066 5.80 -1.33 <0.0001 -0.64 -4.04 0.001 -1.04 -3.73 -1.39 0.0002 -3.85 0.0296 -3.86 0.0005 -0.76 -0.68 0.0464 0.0004 -0.75 0.0438 -4.10 0.0004 -3.99 0.0406 -4.03 0.0001 0.0002 0.0234 0.0283 0.0002 0.0284 Table 86: The average t-statistic. Gene annotations were obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13). Table 87: average t-statistic. Gene annotations were obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Confidential/Proprietary Information -69- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log -0.69-0.69 -4.26 -4.26-0.60 <0.0001 0.02 <0.0001 -4.34 0.02 -0.81 <0.0001 0.0176 -4.78-0.91 <0.0001 -4.97-0.72 0.0103 -0.72 <0.0001 -5.22 0.0046 -5.22 <0.0001 0.0018 <0.0001 0.0018 Log fold change was used to combine probe sets with the same gene symbol prior to the analysis. Results are sorted by descending 2 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tularemia) Day 7 vs. TIV (Influenza) Day 7). The log Gene NameCYP1B1PPIFMAN1A1C11orf96MIR155 Gene Description MIR155HG CLEC5A cytochrome P450, family 1, subfamily B,PRMT10 polypeptide 1 mannosidase,SIK3 peptidylprolyl alpha, isomerase class F 1A, member 1 chromosomePDCD4 11 open reading frame 96ID3GABPB1ELL2 C-type lectin domain family 5, member proteinIGHG2 A arginine methyltransferase 10 (putative)MPHOSPH6GPR84 SIK family programmed kinase cell 3 death 4IL1A (neoplastic transformation inhibitor) GACCRL2 binding protein transcription inhibitor factor, of beta DNA subunitGPR132 binding 1 3, dominant negative helix-loop-helix M-phase proteinADORA2A elongation phosphoprotein factor, 6 RNA -0.74 polymerase II, 2SPECC1L-ADORA2A CYB5D1 G protein-coupled receptor -4.13 84SEC24APHLDA1 interleukin 1, chemokine alpha (C-C motif) receptor-likeFAM177A1 G 2 protein-coupled receptor 132 -0.62 0.0001GAS2L3CTH 0.0223 -0.64 -0.79OLR1 cytochrome -0.61 -4.22 b5 domain containing 1 -0.71PLAU SEC24 family, member A -4.22 (S. -0.63 cerevisiae)C15orf48 pleckstrin -4.35 homology-like -0.70 family domain, -4.37 with family sequence A, similarity member 177,NRIP3 1 0.0001 member -4.31 A1 -0.60 growth -4.13 arrest-specific 0.0218 2 0.0001 -4.29 like 3 <0.0001 <0.0001 0.0234 0.0161 -4.42 0.0141 cystathionase <0.0001 (cystathionine gamma-lyase) oxidized low 0.0161 0.0001 density lipoprotein (lectin-like) 0.0001 receptor plasminogen chromosome 1 activator, 15 urokinase open 0.0228 reading frame 48 0.0211 <0.0001 -0.79 nuclear receptor 0.0136 interactingGene protein Name 3ERV3-2 -4.56GBP5 -0.69 -0.93 -0.86 -4.81 <0.0001 Gene Description 0.0107 -1.00 -0.62 -5.06 -4.85 endogenous -0.75 retrovirus group <0.0001 3, member -5.40 -0.63 2 -0.70 0.0078 -5.18 guanylate binding protein 5 <0.0001 <0.0001 -5.49 -1.54 0.0047 0.006 -5.36 -5.27 <0.0001 <0.0001 0.0023 -0.60 0.0023 -5.72 <0.0001 <0.0001 0.0012 <0.0001 -0.60 -5.62 0.0014 0.0023 -1.51 <0.0001 0.0013 -0.63 -5.57 <0.0001 -5.95 -1.04 0.0013 -5.87 <0.0001 -6.30 0.0014 <0.0001 0.0011 <0.0001 0.0011 <0.0001 0.001 0.64 4.98 0.92 <0.0001 0.0142 4.85 <0.0001 0.0149 Table 88: average t-statistic. Gene annotations were obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Conﬁdential/Proprietary Information -70- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR FC t-Statistic P FDR 2 2 Log 0.690.69 4.32 4.32 <0.0001 0.0189 <0.0001 0.0189 -0.99 -6.35 <0.0001 0.0018 Log 0.850.85 3.89 3.89-0.68-0.96 0.0002 -3.75 0.0002-0.69 0.0321 -3.90-0.69 0.0321 0.0005 -4.03 0.0003 -4.03 0.0472 0.0388 0.0002 0.0002 0.0263 0.0263 fold change was used to combine probe sets with the same gene symbol prior to the analysis. Results are sorted by descending 2 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tularemia) Day 2 vs. LAIV (Inﬂuenza) Day 3). The log Gene NameGBP1P1GABARAPL3GBP4SERPING1OTTHUMG00000159342 Gene Description RP1-93H18.6 GABA(A) receptorsGBP1 guanylate associated binding protein protein like 1, 3, interferon-inducible pseudogene pseudogeneFAM177A1 1OLR1 serpin peptidase inhibitor, clade guanylate G bindingCCRL2 (C1 protein inhibitor), 4 member 1PHLDA1C11orf96CYB5D1 family with sequence similarity guanylate binding 177,NRIP3 protein member 1, A1 interferon-inducibleCYP1B1 oxidized lowFKBP5 density lipoprotein chemokine (lectin-like) (C-C receptor motif) 1 receptor-likeLAMB3 pleckstrin 2 homology-like domain, family A, 0.85 chromosome member 11 1 open reading frame 96 0.78 cytochrome b5 domain containing 1 4.72 nuclear receptor interacting cytochrome protein P450, 3 family 4.64 0.97 1, subfamily B, polypeptide 1 FK506 binding protein 5 laminin, beta <0.0001 3 Gene 4.41 Name 0.0187 <0.0001ST20 0.0187 BTG3CCR3 <0.0001PTGS2 0.0187 -0.61 0.87TCN1 Gene -1.29 Description CLC 0.64 -0.77 -4.06MXD1 3.83 -4.18 suppressorCTB-167B5.2 of tumorigenicity 20 BTG 4.43 -4.64OTTHUMG00000179513 family, member 3 0.0001 chemokine (C-CGABARAPL3 -0.69 motif) receptor 0.0003 prostaglandin-endoperoxide -0.89 3 synthase 0.0001 2 (prostaglandin 0.0317 LOC100996457 G/H -0.64 synthase and 0.0478 cyclooxygenase) transcobalamin 0.0276 <0.0001IL1A I <0.0001 (vitamin B12 -4.36 binding protein, -5.23 0.0187 RJUN 0.0187 binder 1.47 Charcot-Leyden -0.62 family) crystal -4.66 galectin MAX dimerizationCLEC5A protein 1 -0.90 GABA(A) receptors uncharacterizedMIR155 associated LOC100996457 protein like <0.0001 3, -5.12 pseudogene <0.0001 4.19MIR155HG 0.0229 <0.0001 0.0084 -5.22 0.0187 <0.0001 0.0001 interleukin 1, 0.0142 alpha <0.0001 -0.78 C-type lectin 0.0203 jun domain proto-oncogene family 5, 0.0128 member A -5.44 0.77 <0.0001 4.12 0.007 0.64 0.62 0.78 0.0001 3.89 4.73 0.0231 0.66 4.40 2.17 0.0004 <0.0001 4.45 -0.73 0.0443 0.0074 0.89 <0.0001 4.07 0.0144 -3.74 <0.0001 3.90 -0.69 0.0195 0.0003 0.0004 0.0395 -3.99 0.0443 0.0003 0.0399 0.0002 0.0289 Table 89: average t-statistic. Gene annotations were obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Confidential/Proprietary Information -71- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. FC t-Statistic P FDR 2 Log -0.59-0.59 -4.52 -4.52 <0.0001 0.0123 <0.0001 0.0123 -1.08 -6.03 <0.0001 0.0021 Ensembl Gene ID(s) Reactome Pathway(s) Mean LFC Non- Responders Respon- ders -0.5552 -1.12 -0.17 DKFZp667M067) fold change was used to combine probe sets with the same gene symbol prior to the analysis. Results are sorted by descending 2 Differentially expressed genes (vaccine study comparisons, DVC-LVS/USAMRIID-LVS (Tularemia) Day 7 vs. LAIV (Influenza) Day 7). The log Gene NameF3GPR84ADORA2BSLC5A6ADORA2A Gene Description SPECC1L-ADORA2A PRMT10CYP1B1 G adenosine protein-coupled A2b receptor receptor coagulation 84 factorC11orf96 III (thromboplastin, tissue factor)HELZ solute carrier family 5 (sodium-dependentLGALS3 vitamin transporter), member 6FAM177A1 proteinGPR132 arginine methyltransferase 10 (putative)OLR1 cytochrome P450, family 1, subfamily chromosome B,MPHOSPH6 11 polypeptide open 1 reading frame 96PHLDA1 helicaseC15orf48 with lectin, zinc galactoside-binding, family finger with soluble, 3 sequence similarity 177,ABCD3 member -0.59 A1FNIP2 G protein-coupled receptor 132 M-phaseCYB5D1 phosphoprotein 6 -4.47 oxidized lowDCUN1D3 density lipoprotein (lectin-like) receptor 1CCRL2 pleckstrin homology-like domain, family A, chromosome member -0.63LRRC32 15 1 open reading frame <0.0001 48PLAU ATP-binding 0.0127 cassette, sub-family D (ALD),FKBP5 member -4.05 3 folliculin interactingNRIP3 cytochrome protein b5 2 domain DCN1, containing defective 1 in cullinLAMB3 neddylation 1, -0.93 domain containing 3 -0.69 -0.79 0.0002 chemokine (C-C motif) receptor-like leucine 2 rich repeat 0.0287 containing 32 -0.59 -4.55 -4.53 -4.15 plasminogen activator, urokinase FK506 binding protein 5 -4.33 -0.71 -0.71 nuclear receptor <0.0001 interacting protein <0.0001 3 laminin, 0.0001 beta 0.0121 3 0.0123 -1.44 -4.69 0.021 -4.85 -0.68 <0.0001 -0.94 0.0194 -4.94 -4.81 <0.0001 <0.0001 -0.60 -4.99 -0.63 0.0121 -0.60 -0.63 0.0054 <0.0001 <0.0001 -1.38 -5.05 -0.75 0.0054 -5.24 -4.91 -4.69 <0.0001 0.0054 0.0062 -5.03 -4.98 <0.0001 <0.0001 <0.0001 <0.0001 0.005 -0.69 0.0037 0.0054 0.0089 <0.0001 <0.0001 -0.69 -0.97 0.005 0.0054 -5.19 -0.60 -5.07 -5.26 -0.60 <0.0001 0.005 -1.01 -5.27 <0.0001 <0.0001 -5.47 0.005 0.005 -5.77 -0.73 <0.0001 0.0041 <0.0001 -5.47 0.0037 <0.0001 0.0021 <0.0001 0.0025 227029_PM_at FAM177A1 family with sequence similarity 177, member A1 0.3750 -0.59 -0.80 ENSG00000151327 Probe Set ID223767_PM_at Gene1565776_PM_at Name GPR84 Description G protein-coupled receptor 84 Homo sapiens mRNA; cDNA DKFZp667M067 (from clone -0.5811 Coefficient -0.88 Mean LFC -0.04 ENSG00000139572 Table 90: average t-statistic. Gene annotations were obtained from Affymetrix (HT HG-U133 Plus PM Annotations, Release 34,10/24/13).

Conﬁdential/Proprietary Information -72- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. NFKB BY PHOSPHORYLATION ANDIKKS ACTIVATION OF COMPLEX; MAPCASCADE; KINASE JNK C ACTIVATION JUN IN KINASESAND PHOSPHORYLATION TLR ACTIVATION MEDIATED BY ACTIVATED HUMAN TAK1; ACTIVATED TAK1 MEDIATES P38 MAPK ACTIVA- TION; SIGNALING BY ILS; IL1DIATED SIGNALING; ACTIVATION OF IRAK2 TAK1 ME- COMPLEX UPON8 TLR7 OR 9 STIMULATION; TRAF6OF MEDIATED NFKB INDUCTION AND MAP KINASESTIVATION; UPON NFKB TLR7 AND 8 MAP OR KINASES 9 ACTIVATION ME- DIATED AC- BY TLR4 SIGNALINGMAL REPERTOIRE; CASCADE INITIATED MYD88 ONINNATE PLASMA MEMBRANE; IMMUNE SYSTEM;NALLING; IMMUNE ACTIVATED SYSTEM; TLR4 TOLLCADES; RECEPTOR SIG- CAS- NOD1 2SIGNALING IN SIGNALING IMMUNE SYSTEM; PATHWAY; CYTOKINE NUCLEOTIDE BIND- ING DOMAIN LEUCINERECEPTOR RICH NLR SIGNALING REPEAT PATHWAYS CONTAINING OLOGY; SIGNALING BY GPCR; GPVI MEDIATED ACTI- VATION CASCADE; AXON GUIDANCE; GSIGNALLING ALPHA1213 EVENTS; GPCRNALING; DOWNSTREAM SEMA4D SIG- SEMAPHORIN IN INTERACTIONS; SEMAPHORIN SEMA4DCELL MIGRATION INDUCED AND SIGNALING; GROWTHHEMOSTASIS; CONE COLLAPSE; PLATELET ACTIVATIONAND AGGREGATION SIGNALING CEPTOR SIGNALING; ANTIVIRAL MECHANISM BY IFN STIMULATED GENES; SIGNALING BYEASE; FGFR SIGNALING BY IN FGFR1 DIS- BY MUTANTS; SIGNALING FGFR1 FUSION MUTANTS;MUTANTS; SIGNALING SIGNALING BY BY PDGF; DOWNSTREAM FGFR SIG- NAL TRANSDUCTION; SIGNALING BYTION ILS; OF REGULA- IFNGSIGNALING; INTERFERON SIGNALING; ALPHA INTERFERON BETAREGULATION SIGNALING; GAMMA OF IFNASIGNALING; IL SIGNALING; 6 SIGNALING;TOKINE INTERFERON IMMUNE SIGNALING IN SYSTEM; IMMUNE CY- SYSTEM SIGNALING; IMMUNE SYSTEM;ING CYTOKINE IN IMMUNE SIGNAL- SYSTEM SIGNALING; IMMUNE SYSTEM;ING CYTOKINE IN IMMUNE SIGNAL- SYSTEM Ensembl Gene ID(s) Reactome Pathway(s) Mean LFC Non- Responders Respon- ders -0.07970.0769 0.62 0.73 0.94 0.39 STAT1 signal transducer and activator of transcription 1, 91kDa 0.1235 0.90 0.61 ENSG00000115415 SIGNALING BY SCF KIT; GROWTH HORMONE RE- Probe Set ID231779_PM_at Gene Name IRAK2 Description interleukin-1 receptor-associated kinase 2 -0.3229 -0.83 Coefﬁcient -0.30240103_PM_at Mean1564150_PM_a_at LFC 212099_PM_at C12orf79 LOC100996457 ENSG00000134070 uncharacterized LOC100996457 RHOB TRIF chromosome MEDIATED 12 TLR3 open reading SIGNALING; frame 79 TAK1 ACTIVATES ras homolog family member BAFFX-HUMISGF3A /M97935_MA_at 0.2576 0.2122 -0.71 -0.48 -1.27 -0.1781 -0.96 0.49 ENSG00000257242 217502_PM_at 0.86 IFIT2226099_PM_at236439_PM_at 239661_PM_at ENSG00000143878 ELL2232383_PM_at interferon-induced231578_PM_at protein with tetratricopeptide SIGNALING repeats BY 2 RHO GTPASES; DEVELOPMENTAL BI- TFEC 0.1118 GBP1 elongation factor, RNA polymerase II, 2 0.91 transcription factor EC guanylate binding protein 1, interferon-inducible 0.45 0.1084 0.0445 ENSG00000119922 -0.65 INTERFERON ALPHA 1.51 BETA SIGNALING; INTERFERON -0.85 -0.0677 1.03 ENSG00000118985 0.69 ENSG00000117228 INTERFERON 1.21 GAMMA SIGNALING; INTERFERON ENSG00000105967

Confidential/Proprietary Information -73- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. DERMATAN SULFATE METABOLISM; HS GAG BIOSYN- THESIS; HEPARANMETABOLISM; GLYCOSAMINOGLYCAN SULFATE METABOLISM; HEPARINA HS TETRASACCHARIDE GAG LINKERQUIRED SEQUENCE FOR IS GAG RE- CARBOHYDRATES SYNTHESIS; METABOLISM OF HEMOSTASIS INTERFERON ALPHA BETA SIGNALING; INTERFERON SIGNALING; IMMUNE SYSTEM;ING CYTOKINE IN IMMUNE SIGNAL- SYSTEM SIGNALING; IMMUNE SYSTEM;ING CYTOKINE IN IMMUNE SIGNAL- SYSTEM CEPTOR TRANSCRIPTION PATHWAY GLYCOPROTEIN HORMONES; PEPTIDEBIOSYNTHESIS HORMONE Ensembl Gene ID(s) Reactome Pathway(s) Ensembl Gene ID(s) Reactome Pathway(s) Mean LFC Non- Responders Mean LFC Non- Responders Respon- ders Respon- ders -0.2787 -1.080.2087 -0.03 0.84 0.04 0.7756 -0.62 -0.99 microRNA 155,MIR155 host gene (non-protein coding)SFT2 domain containing 3,WD repeat domain 33 -0.6513 -0.80 0.6415 -0.03 -0.60DKFZp667M067) ENSG00000234883 -1.11 ENSG00000136709 MIR155HG WDR33 Combination of genes differentiating between responders and non-responders (Microagglutination titer, Day 2). Selected genes: 19 out of 221563_PM_at204363_PM_at DUSP10240024_PM_at F3 SEC14L2 dual specificity phosphatase 10 SEC14-like coagulation 2 factor (S. III cerevisiae) (thromboplastin, tissue factor) -0.0773 -0.82 -0.1012 -0.68 -0.17 -0.0702 -0.42 -0.77 ENSG00000117525 FORMATION OF ENSG00000143507 FIBRIN -0.21 CLOT CLOTTING CASCADE; ENSG00000100003 206374_PM_at1564093_PM_at240238_PM_at DUSP81557302_PM_at NEK1234632_PM_x_at230218_PM_at ZNF585B212158_PM_at dual specificity phosphatase 8 NIMA-related kinase 1 HIC1 zinc finger protein 585B SDC2 Homo hypermethylated sapiens in cDNA: cancer FLJ22614 1 fis, syndecan clone 2 HSI05089 0.1881 -0.2656 -0.52 -0.79 0.2235 0.2004 -0.85 -0.40 -0.57 -0.1260 0.74 -0.86 ENSG00000184545 -1.07 0.30 -0.1224 -0.26 ENSG00000137601 ENSG00000245680 -1.15 ENSG00000177374 GENERIC TRANSCRIPTION PATHWAY -0.45 ENSG00000169439 HS GAG DEGRADATION; CHONDROITIN SULFATE Probe Set ID203153_PM_at Gene Name IFIT1 Description235175_PM_at GBP4 interferon-induced207978_PM_s_at protein with tetratricopeptide repeats 1227099_PM_s_at NR4A3 -0.0337214059_PM_at guanylate binding protein C11orf96 4 0.62 nuclear receptor IFI44 subfamily 4, group A, member 3 chromosome 11 open reading frame 96 1.03 interferon-induced protein 44 0.0068 Coefficient ENSG00000185745 MeanProbe LFC Set ID -1.66 ANTIVIRAL MECHANISM BY IFN -0.0122 0.0033 STIMULATED GENES; 239567_PM_at -1.88 Gene229437_PM_at 0.74 Name -0.67218851_PM_s_at Description MIR155, ENSG00000119508 -0.0022 1.01 -0.72227140_PM_at SFT2D3, GENERIC TRANSCRIPTION 0.53 NUCLEAR PATHWAY; RE- INHBA ENSG00000187479 223915_PM_at ENSG00000162654232383_PM_at1565776_PM_at 0.83 INTERFERON BCOR GAMMA inhibin, SIGNALING; beta A TFEC INTERFERON ENSG00000137965 BCL6 corepressor transcription factor EC Homo Coefficient sapiens mRNA; cDNA DKFZp667M067 (from clone Mean LFC -0.5637 -0.4996 -0.3052 -0.95 -0.80 0.65 -0.15 -0.31 1.17 ENSG00000122641 ENSG00000183337 METABOLISM ENSG00000105967 OF AMINO ACIDS AND DERIVATIVES; Table 91: 117, minimum mean deviance:are 1.14, based mean on misclassification Affymetrix error:4.0). HG-U133 0.26). Plus Sorted Perfect Match by Release absolute 34. logistic regression Pathway coefficient. annotations are Probe Set based annotations on Reactome classifications (MSigDB Version

Confidential/Proprietary Information -74- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. NALING; TGF BETAVATES SMADS; SIGNALING RECEPTOR BY TGF SIGNALING BETA RECEPTOR COMPLEX ACTI- TEM; CYTOKINE SIGNALING IN IMMUNE SYSTEM ING RECEPTORS;RECEPTORS; CLASS A1 CHEMOKINECHEMOKINES; RHODOPSIN GPCR RECEPTORS LIKE G DOWNSTREAM ALPHA SIGNALING; BIND IBINDING SIGNALLING EVENTS; GPCR LIGAND OF NUCLEOTIDES; G1 SG1 TRANSITION; S MITOTIC G1 PHASES;DNA REPLICATION; G1 E2F S SPECIFIC TRANSCRIPTION; MEDIATEDPYRIMIDINE METABOLISM REGULATION OF SIGNALING; NEGATIVE REGULATION OF FGFRNALING; ARMS SIG- MEDIATED ACTIVATION; PROLONGED ERK ACTIVATION EVENTS;TRKA FROM NGF THE PLASMA SIGNALLING MEMBRANE;TO SIGNALLING VIA ERKS; SIGNALINGNALLING BY TO FGFR P38 IN VIAACROSS RIT DISEASE; CHEMICAL AND SIG- RIN; SYNAPSES; TRANSMISSION TEM; NEURONAL NEUROTRANSMITTER SYS- AND RECEPTOR DOWNSTREAM TRANSMISSION BINDING INSYNAPTIC CELL; THE ACTIVATION POST- OF NMDAUPON RECEPTOR GLUTAMATE BINDINGEVENTS; AND CREB PHOSPHORYLATION POSTSYNAPTIC THROUGH THE ACTIVATION OF RAS; POST NMDAVATION RECEPTOR EVENTS; ACTI- SIGNALING BY FGFR TRIX ORGANIZATION;TIONS CELL AT THE SURFACE VASCULARMATION; INTERAC- WALL; PLATELET COLLAGEN ADHESION FOR- TOLAGEN; EXPOSED INTEGRIN COL- CELLSIGNALING SURFACE INTERACTIONS; BYTION PDGF; CASCADE; GPVI AXONACTIONS; GUIDANCE; MEDIATED NCAM1 NCAM INTER- ACTIVA- SIGNALINGGROWTH; HEMOSTASIS; PLATELET ACTIVATION SIG- FOR NEURITENALING AND AGGREGATION OUT Ensembl Gene ID(s) Reactome Pathway(s) Mean LFC Non- Responders Respon- ders 0.0103 -0.69 -0.78 0.0345 -0.51 -1.04 SQ SEQUENCE CONTAMINATION WARNING(H.sapiens) ENTRY 223767_PM_at202014_PM_at GPR84 PPP1R15A protein phosphatase G 1, protein-coupled regulatory receptor 84 subunit 15A -0.0076 -0.90 -0.0101 -0.33 -1.11 ENSG00000087074 -0.31 DOWNREGULATION OF TGF BETA RECEPTOR SIG- ENSG00000139572 Probe Set ID238756_PM_at Gene204103_PM_at Name212659_PM_s_at GAS2L3 Description CCL4207850_PM_at IL1RN growth arrest-specific 2 like 3 CXCL3 chemokine interleukin (C-C 1 motif) receptor ligand antagonist 4244026_PM_at chemokine (C-X-C motif) ligand201490_PM_s_at 3208868_PM_s_at202589_PM_at PPIF GABARAPL1 GABA(A) TYMS receptor-associated protein like -0.0544 1 peptidylprolyl -0.0429 isomerase F -0.0543236402_PM_at Coefficient -0.97 -0.0408 thymidylate synthetase Mean -0.92 -0.85 LFC BRAF -1.33 0.0325 -0.43 -0.36 -0.28 v-raf murine -0.60 sarcoma viral -0.38 oncogene ENSG00000139354 homolog B1 ENSG00000136689 ENSG00000275302 -0.78 -0.0333 SIGNALING ENSG00000163734 BY ILS; 0.0190 IL1 SIGNALING; IMMUNE -0.94 SYS- SIGNALING 0.0316 ENSG00000139112 BY GPCR; -0.69 PEPTIDE1556499_PM_s_at LIGAND BIND- -0.50 0.77 COL1A1 -0.79 ENSG00000108179 0.43 collagen, type I, alpha 1 ENSG00000157764 SIGNALLING ENSG00000176890 BY NGF; SPRY REGULATION OF206173_PM_x_at FGF CELL CYCLE;237496_PM_at CELL CYCLE MITOTIC; GABPB1 METABOLISM GA binding protein transcription factor, beta subunit 1 -0.0126 0.0114 -1.01 ESTs, Weakly similar to ALU7HUMAN ALU SUBFAMILY -0.63 -0.54 -0.84 ENSG00000108821 DEVELOPMENTAL ENSG00000104064 BIOLOGY; EXTRACELLULAR MA-

Confidential/Proprietary Information -75- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Mean Explained Variance (IMO Variables, C1+C2) Mean Explained Variance (Gene Variables, C1+C2) Ensembl Gene ID(s) Reactome Pathway(s) Canonical Correlation (C2) Mean LFC Non- Responders Correlation (C1) Respon- ders CV Canonical IMO Variables Canonical correlation analysis summary statistics Variables Table 93: 37 5338 11738 5 21939 5 291 5 0.69 0.66 0.30 5 0.60 0.14 0.42 0.99 0.27 0.49 0.89 0.33 0.98 0.23 0.87 0.04 0.72 0.08 0.70 0.75 0.71 Treatment Group N Gene Groups Groups Groups Groups Study Visit Day 1Day Combined 2 Study Day Combined 7 Study Day Combined 14 Study Combined Study Combination of genes differentiating between responders and non-responders (Microagglutination titer, Day 7). Selected genes: 31 out of Probe Set ID Gene Name Description Coefficient Mean LFC Table 92: 219, minimum mean deviance:are 0.96, based mean on misclassification Affymetrix error:4.0). HG-U133 0.21). Plus Sorted Perfect Match by Release absolute 34. logistic regression Pathway coefficient. annotations are Probe Set based annotations on Reactome classifications (MSigDB Version

Conﬁdential/Proprietary Information -76- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

Figures

DVC−LVS (42 Significant Genes, Day 7)

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● ● −1.5 ● ● Log Fold Change (USAMRIID−LVS) Log Fold

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Log Fold Change (DVC−LVS)

USAMRIID−LVS (103 Significant Genes, Day 14)

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Log Fold Change (USAMRIID−LVS)

Figure 1: Scatter plot of fold changes of signiﬁcant genes (DVC-LVS vs. USAMRIID-LVS, Day 7, 14). Fold change region in which both study groups exceed the upper fold change cut off is shaded in red. Fold change region in which both study groups are below the lower fold change cut off is shaded in green

Conﬁdential/Proprietary Information -77- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

Gene cluster dendrogram with bootstrap probabilities (Combined Study Groups, Day 1−14) 1.5

1.0 99 0 0 65 0 79 0 48 39 0 74 0 0 0 0 0 0 0 0 0 PDK4* 0 0 50 39 98 0 66 46 87 0 0 58 0 73 0 0 0 0 0 0

0.5 0 48 0 83 89 0 97 58 37 0 0 88 55 45 64 0 0 82 0 89 93 0 0 0 84 0 0 75 0 88 62 0 0 68 0 95 0 64 6547 77 86 67 100 0 60 0 0 40 0 0 0 73 83 60 94 0 88 71 86 90 63 81 60 70 79 0 81 0 98 0 80 43 0 42 49 0 0 0 87 64 64 94 64 067 0 84 92 83 87 77 34 49 72 75 74 73 93 0 0 66 76 69 0 74 61 77 62 0 90 66 62 0 96 95 84 65 82 83 50 78 0 84 88 RHOB* 53 90 46 60 67 66 94 85 58 88 995950 47 66 83 0 100 81 48 75 75 78 63 90 88 78 0 48 0 0 71 89 91 70 63 55 76 100 66 69 91 99 68 55 0 75 98 90 81 64 79 0 94 91 99 69 92 65 84 89 82 9077 90 73 62 35 94 94 70 60 0 97 0 76 94 AFF4* 85 89 85 94 90 99 91 71 90 77 94 99 66 83 73 92 84 80 86 97 94 236439_PM_at*

89 MRVI1* 92 83 83 73100 83 0 70 85 65 89 98 95 72 85 88 7467 87 75 97 70 94 89 86 CLC* 92 95 98 97 88 CCR3* 82 66 85 89 84 69 0 100 85 87 99 77 93 87 93 79 97 IFI44* 63 63 65 85 92 85 95 239661_PM_at* 93 8354 8172 79 87 8263 86 55 67 100 94 79 99 90 94 98 9179 94 91100 71 94 66 97 99 100 BCOR* 77 71 79 46 81 85 ST20*

96 97 100 232958_PM_at* 77 92 89 CCR6* 68 97 100 92 74 85 88 57 86 89 243736_PM_at* 82 100 8893 97 95 95 100 64 1566501_PM_at* TYMS (1554696_PM_s_at)*

86 67 SGMS2* 96 ID3* 96 84

78 99 1563509_PM_at* 100 96 92 82 76 99 96 87 73 100 GBP1P1* 100 98 91 98 ZC3HAV1L* 80 99 79 242058_PM_at* 97

77 99 IFI44L* 96 PLAU* 100 99 100

ZNF165* 100 MIR155,MIR155HG*

100 244044_PM_at*

100 HIC1* 100 TRIOBP* 99

95 100 TNF*

99 95 100 LOC283788*

HIVEP1* 98 100 62 1554948_PM_at* RRM2 (201890_PM_at)* KIAA0101* 62 SLC38A9*

100 MS4A14* DHRS9* 100 CD44* CNOT6L* FGF9* 238645_PM_at* FAR2* BMP2K* 220612_PM_at* CDC42* INHBA* CEP19* CTH* RGS13* KMO* 228455_PM_at* OR52K3P* ATG4C* 224098_PM_at* 231484_PM_at* LCP2* NFATC3* TMEM52B* IRAK2* SASH1* TNFRSF21* ZNF10* SPIN3* IL1R1* 239301_PM_at* TNFAIP6* GAS2L3* ZNF585B* NLRC4* 0.0 HERC4* CXCL3* HGF* C11orf96* PMP22* MS4A4A* MN1* ATF3* ZDBF2* STX7* SFT2D3,WDR33* LRRC32* SEC14L2 (204541_PM_at)* JAK2* JAG1* 1564430_PM_at* GBP1 (231578_PM_at)* TYMS (202589_PM_at)* F3* LINC00877* DUSP16* IFI35* WARS* PID1* AP1G1* ARMC8* SLAMF8* OAS2* 1562289_PM_at* POLI* TNFRSF17* 1563621_PM_at* MPHOSPH6* SERPING1* MAFB* GABPB1* 237204_PM_at* ZNF207* RGCC* VPS41* IFIT1* CBR4* HERC3* DUSP8* C9orf69* TSC22D2* ENC1* SKIL* BAIAP2−AS1* NEK1* GBP4 (235574_PM_at)* SLC5A6* 243605_PM_at* 235286_PM_at* MYOF (217518_PM_at)* MYOF CREB5* CASS4* 1570432_PM_at* GPR84* GCNT7* PCMTD1* THBS1* TLR7* HCAR3* 216050_PM_at* COL1A1* 244298_PM_at* ZFYVE16* MS4A6A* PHC3* RRM2 (209773_PM_s_at)* AVPI1* CCDC174* SIK3* RBM33 (1554096_PM_a_at)* 1565776_PM_at* 232375_PM_at* 241970_PM_at* SNX9* FCRL3* PHF20L1* BTBD19* SDC2* LAMB3* IFNAR1* 1561738_PM_at* 241917_PM_at* ARL5B* IFIT2 (217502_PM_at)* PDCD4* MS4A7* ZNF184* KDM6B* OTTHUMG00000184015,RP6−99M1.2* PTX3* GTF2H1* CCL4* RNF213* LOC100131067* CXCL10* 227333_PM_at* GBP4 (235175_PM_at)* DDX60* NUP98* AIM2* CXCR2* USP36 (1554836_PM_at)* SMAD7* LDLR* 238653_PM_at* IER3* ICAM1 (215485_PM_s_at)* HBD* C12orf79* 1565701_PM_at* TLR5* 237496_PM_at* 240207_PM_at* FCGR3B* LMNA (1554600_PM_s_at)* RNMT* ETNK1* 233309_PM_at* METTL3* GIMAP8* JMY* CXCL2* SEC14L2 (240024_PM_at)* PHLDA2* 241740_PM_at* PDE4D (211840_PM_s_at)* EIF4E* 239567_PM_at* SAP30L* SMCO4* HSPA1A,HSPA1B* PDE4B* PLAUR* LOC101060521,POLR3E* OLR1* DDX58 (222793_PM_at)* GPR132* ZNF571* NLRP3* THAP2* SAMD4A* LOC100996457* RGS1* CCRL2* SOS1* ARAF* METRNL* 242598_PM_at* GIMAP1* 232406_PM_at* CA1* IL1A* JUN (201465_PM_s_at)* JUN (201466_PM_s_at)* 244868_PM_at* TNFRSF10C* FOSL2* NUPL1* C15orf48* ABCA1 (216066_PM_at)* ANKRD22 (239196_PM_at)* 240238_PM_at* JMJD6* LOC284837* PPP1R16B* SC5D* NAMPT* USP36 (224979_PM_s_at)* CCR2* VPS35* RAB10* MEF2C* PARP9 (227807_PM_at)* PARP9 GAPT* 239876_PM_at* SLC7A5* FAM177A1* B3GNT5* HDHD2* CREB5,LOC401317* MAP3K8* CCL20* 244054_PM_at* KBTBD8* PHACTR1* CX3CR1* LOC100996870* 230918_PM_at* 224989_PM_at* TNFAIP8L2* ARFIP1* 243771_PM_at* DDIT3* PRMT10* TP53INP2* GIMAP4* KRCC1* SLC4A1* SERTAD1* SLC35B3* 215630_PM_at* OTTHUMG00000159342,RP1−93H18.6* TRIM69* ATP10D* 232000_PM_at* SERPINB2* 240061_PM_at* SAMSN1* 227618_PM_at* 233121_PM_at* NRIP3 (222900_PM_at)* RASGEF1B* ST8SIA4 (230836_PM_at)* FCGR3A,FCGR3B* 231972_PM_at* ANKRD22 (238439_PM_at)* RBM33 (1554095_PM_at)* SYTL3 (1561882_PM_at)* 243659_PM_at* 233127_PM_at* SYTL3 (1562255_PM_at)* ABCG1 (232081_PM_at)* PARP9 (223220_PM_s_at)* PARP9 EPSTI1 (235276_PM_at)* 230233_PM_at* DUSP10 (221563_PM_at)* OTTHUMG00000178354,RP11−769O8.3* 233674_PM_at* ABCG1 (204567_PM_s_at)* 227052_PM_at* IGLV2−14,IGLV2−14* HES1 (203394_PM_s_at)* HES1 (203395_PM_s_at)* 229670_PM_at* TFEC (232383_PM_at)* LMNA (203411_PM_s_at)* LMNA (212086_PM_x_at)* TRDC,TRDC* RGS16 (209324_PM_s_at)* RGS16 (209325_PM_s_at)* THBD (237252_PM_at)* IFIT3 (204747_PM_at)* 1569477_PM_at* 239451_PM_at* BRAF (236402_PM_at)* BRAF (243829_PM_at)* MYOF (201798_PM_s_at)* MYOF (211864_PM_s_at)* MYOF CTB−167B5.2,OTTHUMG00000179513* ADORA2A,SPECC1L−ADORA2A* DUSP10 (215501_PM_s_at)* 226397_PM_s_at* TFEC (236995_PM_x_at)* DOCK4 (1558691_PM_a_at)* DDX58 (218943_PM_s_at)* STAT1 (AFFX−HUMISGF3A/M97935_5_at)* STAT1 CYB5D1 (226833_PM_at)* SAMD9L (235643_PM_at)* SPTLC2 (225095_PM_at)* EMP1 (201324_PM_at)* SPTLC2 (203128_PM_at)* PAQR8 (226423_PM_at)* PAQR8 (227626_PM_at)* PAQR8 EPSTI1 (227609_PM_at)* USP36 (220370_PM_s_at)* 235592_PM_at* 240038_PM_at* ST8SIA4 (230261_PM_at)* ST8SIA4 (242943_PM_at)* OTTHUMG00000173015,RP1−239B22.5* IL1RN (212659_PM_s_at)* IL1RN (216243_PM_s_at)* OAS1 (202869_PM_at)* OAS1 PDE4D (210836_PM_x_at)* PPIF (201489_PM_at)* FCGR1B,FCGR1C* IFIT2 (226757_PM_at)* IFIT3 (229450_PM_at)* DOCK4 (244840_PM_x_at)* GBP5 (229625_PM_at)* GBP5 (238581_PM_at)* C10orf137 (208115_PM_x_at)* C10orf137 (215072_PM_x_at)* EMP1 (201325_PM_s_at)* DUSP4 (204015_PM_s_at)* PHLDA1 (217999_PM_s_at)* PHLDA1 YES1 (202932_PM_at)* USP36 (227093_PM_at)* CYB5D1 (1552711_PM_a_at)* OAS1 (205552_PM_s_at)* OAS1 MOSPD2 (64883_PM_at)* PPIF (201490_PM_s_at)* ELL2 (226099_PM_at)* ELL2 (226982_PM_at)* USP36 (224978_PM_s_at)* SAMD9L (230036_PM_at)* GBP1 (202270_PM_at)* IDH1 (201193_PM_at)* DUSP4 (204014_PM_at)* DUSP4 (226034_PM_at)* NRIP3 (219557_PM_s_at)* MOSPD2 (221895_PM_at)* PDE4D (210837_PM_s_at)* YME1L1 (213830_PM_at)* YES1 (202933_PM_s_at)* PHLDA1 (217998_PM_at)* PHLDA1 (225842_PM_at)* PHLDA1 TCL1A (39318_PM_at)* RANBP2 (226922_PM_at)* PDE4D (204491_PM_at)* ABCA1 (203505_PM_at)* ZBTB21 (225539_PM_at)* ICAM1 (202637_PM_s_at)* ICAM1 (202638_PM_s_at)* SAMD9L (226603_PM_at)* RANBP2 (201712_PM_s_at)* TNFSF10 (214329_PM_x_at)* IDH1 (1555037_PM_a_at)* THBD (203888_PM_at)* MAFF (36711_PM_at)* ZBTB10 (219312_PM_s_at)* ZBTB10 (233899_PM_x_at)* IL1B (39402_PM_at)* TNFSF10 (202688_PM_at)* ABCA1 (203504_PM_s_at)* ZBTB21 (233952_PM_s_at)* MAFF (205193_PM_at)* TCL1A (209995_PM_s_at)* NR4A3 (209959_PM_at)* PHLDA1 (217996_PM_at)* PHLDA1 (217997_PM_at)* PHLDA1 IL1B (205067_PM_at)* THBD (203887_PM_s_at)* CREM (230511_PM_at)* ZNF331 (219228_PM_at)* ZNF331 (227613_PM_at)* FCGR1A,FCGR1B,FCGR1C* GBP1 (202269_PM_x_at)* GBP1 (231577_PM_s_at)* TNFSF10 (202687_PM_s_at)* CREM (214508_PM_x_at)* CYP1B1 (202437_PM_s_at)* OTTHUMG00000175937,RP11−425D10.10* NR4A3 (207978_PM_s_at)* YME1L1 (216191_PM_s_at)* PPP1R15A (37028_PM_at)* GABARAPL1 (208868_PM_s_at)* GABARAPL1 (208869_PM_s_at)* CREM (207630_PM_s_at)* CREM (209967_PM_s_at)* PPP1R15A (202014_PM_at)* CYP1B1 (202435_PM_s_at)* CYP1B1 (202436_PM_s_at)* STAT1 (AFFX−HUMISGF3A/M97935_MA_at)* STAT1 (AFFX−HUMISGF3A/M97935_MB_at)* STAT1 IGLJ2,IGLJ2,IGLJ3,IGLJ3,IGLV2−14,IGLV2−14*

Figure 2: Gene cluster dendrogram with bootstrap probabilities (Combined Study Groups, Day 1-14). The y axis shows the distance at which clusters were formed by the complete linkage clustering algorithm based on uncentered Pearson correlation distance between log fold changes. Multiscale bootstrap probabilities are shown at each branch intersection. Signiﬁcant clusters are highlighted in blue.

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Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−001 (n=2) CALLD1D14−002 (n=2) CALLD1D14−003 (n=2) CALLD1D14−004 (n=2) CALLD1D14−005 (n=2)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS 1 1 1 1 1

0 ● 0 0 0 ● 0 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● −1 −1 ● −1 −1 ● −1 ● ● ● Mean LogFC Mean LogFC Mean LogFC Mean LogFC

●

−2 Genes: −2 Genes: −2 Genes: −2 Genes: −2 Genes: ● *IL1B (205067_PM_at) *MAFF (205193_PM_at) *PPP1R15A (202014_PM_at) *235592_PM_at *NR4A3● (207978_PM_s_at) *IL1B (39402_PM_at) *MAFF (36711_PM_at) *PPP1R15A (37028_PM_at) *240038_PM_at *NR4A3 (209959_PM_at) Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−006Study Visit Day (n=3) CALLD1D14−007Study Visit Day (n=2) CALLD1D14−008Study Visit Day (n=2) CALLD1D14−009Study Visit Day (n=2) CALLD1D14−010Study Visit Day (n=2)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS

1 1 1 ● 1 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0 0 0 0 0

● ● ● ● ● ● ● ● ● ●

−1 −1 −1 −1 ● −1 ● ● ● ● ● Mean LogFC Mean LogFC Mean LogFC Mean LogFC Genes:

−2 *CYP1B1 (202435_PM_s_at) −2 Genes: −2 Genes: −2 Genes: −2 Genes: *CYP1B1 (202436_PM_s_at) *TCL1A (209995_PM_s_at) *FCGR1B,FCGR1C *DDIT3 *IDH1 (1555037_PM_a_at) *CYP1B1 (202437_PM_s_at) *TCL1A (39318_PM_at) *FCGR1A,FCGR1B,FCGR1C *239451_PM_at *IDH1 (201193_PM_at) Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−011Study Visit Day (n=2) CALLD1D14−012Study Visit Day (n=2) CALLD1D14−013Study Visit Day (n=3) CALLD1D14−014Study Visit Day (n=2) CALLD1D14−015Study Visit Day (n=2)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS

● ● 1 1 1 1 1

● ● ● ● ● ● ● ● ● ● ● ● ● ●

0 0 ● 0 0 0 ● ● ● ● ● ● ● ● ● ● ● ● ● −1 −1 −1 −1 −1 ● ● ● ●

Mean LogFC Mean LogFC Mean LogFC Mean LogFC ● Genes: ●

−2 Genes: −2 Genes: −2 *GBP1 (202269_PM_x_at) −2 Genes: −2 ● Genes: *KRCC1 *1569477_PM_at *GBP1 (202270_PM_at) *ZBTB10 (219312_PM_s_at) *CCL20 *229670_PM_at *233674_PM_at *GBP1 (231577_PM_s_at) *ZBTB10 (233899_PM_x_at) *IL1A Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−016Study Visit Day (n=2) CALLD1D14−017Study Visit Day (n=2) CALLD1D14−018Study Visit Day (n=2) CALLD1D14−019Study Visit Day (n=2) CALLD1D14−020Study Visit Day (n=3)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS 1 1 1 1 1

0 0 ● 0 0 0

● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

−1 −1 −1 ● ● ● −1 ● −1 ● ● ● ● ● ● ● ● ● Mean LogFC Mean LogFC Mean LogFC Mean LogFC ● Genes:

−2 Genes: −2 Genes: −2 Genes: −2 Genes: −2 *SERPINB2 *RANBP2 *GABARAPL1 (208868_PM_s_at) *PHLDA1 (217998_PM_at) *RASGEF1B *PHLDA1 (217996_PM_at) *PRMT10 *GABARAPL1 (208869_PM_s_at) *PHLDA1 (225842_PM_at) *230233_PM_at *PHLDA1 (217997_PM_at) Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day

Figure 3: Gene cluster time trends of baseline log2 fold change by study group (Combined Study Groups, Day 1-14). Header indicates cluster ID. Mean log2 fold change across cluster genes is drawn in bold. Individual mean gene log2 fold changes are plotted in lighter colors.

Conﬁdential/Proprietary Information -79- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−021 (n=3) CALLD1D14−022 (n=2) CALLD1D14−023 (n=2) CALLD1D14−024 (n=3) CALLD1D14−025 (n=2)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS

1 1 1 1 ● ● 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0 0 0 0 0 ● ● ● ● ● ● ● ● −1 −1 −1 −1 −1 Mean LogFC Mean LogFC Mean LogFC Mean LogFC Genes: Genes:

−2 *YME1L1 (213830_PM_at) −2 Genes: −2 Genes: −2 *TNFSF10 (202687_PM_s_at) −2 Genes: *YME1L1 (216191_PM_s_at) *RANBP2 *GBP5 (229625_PM_at) *TNFSF10 (202688_PM_at) *MOSPD2 (221895_PM_at) *TRDC,TRDC *KBTBD8 *GBP5 (238581_PM_at) *TNFSF10 (214329_PM_x_at) *MOSPD2 (64883_PM_at) Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−026Study Visit Day (n=2) CALLD1D14−027Study Visit Day (n=2) CALLD1D14−028Study Visit Day (n=3) CALLD1D14−029Study Visit Day (n=2) CALLD1D14−030Study Visit Day (n=4)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS

1 ● 1 1 1 ● 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0 0 0 0 0 ● ● ● ● ● ● ● ● ● −1 −1 −1 −1 −1

Mean LogFC Mean LogFC Mean LogFC Mean LogFC Genes: Genes: *TRIM69

−2 Genes: −2 Genes: −2 *SLC4A1 −2 Genes: −2 *AIM2 *STAT1 (AFFX−HUMISGF3A/M97935_MA_at) *EMP1 (201324_PM_at) *CA1 *SAMD4A *SAMD9L (226603_PM_at) *STAT1 (AFFX−HUMISGF3A/M97935_MB_at) *EMP1 (201325_PM_s_at) *HBD *EPSTI1 *SAMD9L (230036_PM_at) Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−031Study Visit Day (n=2) CALLD1D14−032Study Visit Day (n=3) CALLD1D14−033Study Visit Day (n=2) CALLD1D14−034Study Visit Day (n=2) CALLD1D14−035Study Visit Day (n=3)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS 1 1 1 1 1 ● ● ● ● ● ● ● ●

● 0 0 0 0 0 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● −1 −1 −1 −1 −1 Mean LogFC Mean LogFC Mean LogFC Mean LogFC Genes: Genes:

−2 Genes: −2 *THBD (203887_PM_s_at) −2 Genes: −2 Genes: −2 *ABCA1 (203504_PM_s_at) *IL1RN (212659_PM_s_at) *THBD (203888_PM_at) *CYB5D1 (1552711_PM_a_at) *224989_PM_at *ABCA1 (203505_PM_at) *IL1RN (216243_PM_s_at) *THBD (237252_PM_at) *CYB5D1 (226833_PM_at) *SAMD9L *SDC2 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−036Study Visit Day (n=4) CALLD1D14−037Study Visit Day (n=2) CALLD1D14−038Study Visit Day (n=2) CALLD1D14−039Study Visit Day (n=5) CALLD1D14−040Study Visit Day (n=2)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS

1 1 1 1 ● 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

0 0 0 ● 0 0 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● −1 −1 −1 −1 −1

Genes: Genes: Mean LogFC Mean LogFC Mean LogFC *TLR5 Mean LogFC *LOC284837 *SLC35B3

−2 *OAS1 (202869_PM_at) −2 Genes: −2 Genes: −2 *HDHD2 −2 Genes: *SPTLC2 *LMNA (203411_PM_s_at) *HES1 (203394_PM_s_at) *227618_PM_at *OTTHUMG00000175937,RP11−425D10.10 *OAS1 (205552_PM_s_at) *LMNA (212086_PM_x_at) *HES1 (203395_PM_s_at) *242598_PM_at *239567_PM_at Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day

Figure 4: Gene cluster time trends of baseline log2 fold change by study group (Combined Study Groups, Day 1-14). Header indicates cluster ID. Mean log2 fold change across cluster genes is drawn in bold. Individual mean gene log2 fold changes are plotted in lighter colors.

Conﬁdential/Proprietary Information -80- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−041 (n=2) CALLD1D14−042 (n=2) CALLD1D14−043 (n=2) CALLD1D14−044 (n=13) CALLD1D14−045 (n=2)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS 1 1 1 1 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

0 0 0 0 Genes: 0 *CX3CR1 ● ● ● *CCR2 ● ● *MEF2C ● *GIMAP4 *TLR7 −1 −1 −1 −1 *VPS35 −1 *RAB10 *TNFAIP8L2 Mean LogFC Mean LogFC Mean LogFC *SPTLC2 Mean LogFC *TFEC (232383_PM_at)

−2 Genes: −2 Genes: −2 Genes: −2 *GIMAP8 −2 Genes: *MS4A6A *CREB5 *SLC5A6 *TFEC (236995_PM_x_at) *PARP9 *POLI *CREB5,LOC401317 *DUSP8 *LOC100996870 *232375_PM_at Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 Combined Study Groups, Day 1−14 CALLD1D14−046Study Visit Day (n=3) CALLD1D14−047Study Visit Day (n=2) CALLD1D14−048Study Visit Day (n=3) CALLD1D14−049Study Visit Day (n=3) CALLD1D14−050Study Visit Day (n=13)

2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS 2 DVC−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS USAMRIID−LVS 1 1 1 1 1 ● ● ● ● ● ● ● ● ● ● ● ● ● ● 0 0 0 0 ● 0 Genes: ● ● ● ● *C12orf79 ● ● ● ● *YES1 (202932_PM_at) ● ● ● ● ● ● ● ● *YES1● (202933_PM_s_at) ● ● ● ● *ABCG1● (204567_PM_s_at) *GABPB1 −1 −1 −1 −1 −1 *NUP98 *PPP1R16B *220612_PM_at Mean LogFC Mean LogFC Mean LogFC Mean LogFC *SNX9 Genes: Genes: Genes: *USP36

−2 *TNFRSF17 −2 Genes: −2 *NFATC3 −2 *1564430_PM_at −2 *ELL2 (226099_PM_at) *IGLJ2,IGLJ2,IGLJ3,IGLJ3,IGLV2−14,IGLV2−14 *1565776_PM_at *RNF213 *JUN (201465_PM_s_at) *ELL2 (226982_PM_at) *IGLV2−14,IGLV2−14 *ABCA1 *240238_PM_at *JUN (201466_PM_s_at) *ABCG1 (232081_PM_at) Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day 1 Day 2 Day 7 Day Day 14 Day 14 Day 14 Day 14 Day 14 Day Combined Study Groups, Day 1−14 CALLD1D14−051Study Visit Day (n=4) Study Visit Day Study Visit Day Study Visit Day Study Visit Day

2 DVC−LVS USAMRIID−LVS

1 ● ● ● ● ● ●

0 ● −1

Genes: *RRM2 (201890_PM_at)

−2 *KIAA0101 *TYMS *RRM2 (209773_PM_s_at) Day 1 Day 2 Day 7 Day Day 14 Day Study Visit Day Figure 5: Gene cluster time trends of baseline log2 fold change by study group (Combined Study Groups, Day 1-14). Header indicates cluster ID. Mean log2 fold change across cluster genes is drawn in bold. Individual mean gene log2 fold changes are plotted in lighter colors.

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DVC−LVS / USAMRIID−LVS (Tularemia)

1.5 YF−17D (Yellow Fever) ● A TIV (Influenza) LAIV (Influenza)

Genes: IFI44L GBP1P1

1.0 IFI44 IFIT1 EPSTI1 IFIT3 CMPK2 RSAD2 ● OAS3 IFIT2 IFI6 TNFSF10 MX1 AIM2 ● ISG15 MYOF Fold Change Fold IRF7 TFEC 2

0.5 SIGLEC1 SMCO4 USP18 IDH1 SERPING1 LOC284837 ● ● HERC6 XAF1 ● LAMP3 OAS2 LOC200772 OAS1 ● LINC00487 SAMD9L GBP1 DDX60

Mean Log STAT1 IFI35 0.0 PARP9 RP11−769O8.3 ● WARS OTTHUMG00000159342 FCGR1B SASH1 FCGR1C FANCL GBP4 GAPT GBP5 RAB10 ANKRD22 GIMAP4 CXCL10 CCR2 −0.5

2/3 7 Post−treatment Day

DVC−LVS / USAMRIID−LVS (Tularemia) YF−17D (Yellow Fever) B TIV (Influenza) LAIV (Influenza) ● 1.0 Fold Change Fold 2

0.5 Genes: IGLJ2 OTTHUMG00000153338 IGLJ3 AC016745.2 IGLV1−44 IGK IGLV1−36 IGKC

● IGLV1−50 IGKV1−17 Mean Log ● IGHV4−31 IGKV1D−37 ● ● ● IGHG3 IGKV1−37 IGHM TNFRSF17 ● IGHA2 MZB1 ● IGHV3−23 IGJ

0.0 IGHD CD38 IGHG2 IGLV3−10 IGLV2−14 IGLV3−1 IGLL3P IGLV3−19

2/3 7 Post−treatment Day

1.5 DVC−LVS / USAMRIID−LVS (Tularemia) YF−17D (Yellow Fever) ● C TIV (Influenza) LAIV (Influenza)

1.0 Genes: IFI44L PGAP1 CXCL10 IFI44 IFI27 APOL6 CMPK2 LINC00487 PARP14 EPSTI1 LY6E IFI35 OAS3 KLHDC7B RNF213 ● IFIT1 LGALS3BP FBXO6 RSAD2 ZBP1 MYOF MX1 FAM225B SLC27A3 Fold Change Fold

0.5 ISG15 FAM225A HPSE 2 IFI6 TYMP SASH1 ● IRF7 LGALS9 FCGR1B SERPING1 NAPA FCGR1C SAMD4A CTSL1 ANKRD22 SIGLEC1 CCR1 WARS ● ● ● USP18 MAFB DDX60L LAMP3 XK MARCKS ● HERC6 TMEM140 PLSCR1 Mean Log

0.0 SPATS2L GMPR SP100 RGL1 XAF1 C3AR1

● IFIT3 OAS2 RIN2 IFIT2 SAMD9L TCF7L2 OASL MS4A4A CDKN1C FAM46A NEXN LOC200772 IFIH1 GBP1 C1QA EIF2AK2 STAT1 CLEC4F KIAA1958 PARP9 −0.5 2/3 7 Post−treatment Day

Figure 6: Time trends of mean log2 fold change and associated 95% bootstrap confidence intervals for gene clusters identified in subject-level heatmaps. Confidential/Proprietary Information -82- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

CD3+ CD4+ CD38+ HLA−DR+ T−cell activation (n=35) 35 30 25 Responder

20 Persistent Responder Transient Responder 15

Subjects Non responder 10 5

● 0

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Standard deviation cut off CD3+ CD8+ CD38+ HLA−DR+ T−cell activation (n=35)

35 Responder

30 Persistent Responder Transient Responder

25 Non responder 20 15 Subjects 10 5

● 0

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Standard deviation cut off Tularemia−specific microagglutination titer (n=35) 35 30 25

20 Responder Non responder 15 Subjects 10 5

● 0

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Standard deviation cut off

Figure 7: Number of subjects with microarray data for all post-vaccination days that pass a certain immune response cut off by assay. Y-axis: number of subjects, x-axis: the number of standard deviations above the baseline mean used to deﬁne responders (see Section 2.8 for details). The dashed black vertical line indicates the standard deviation cut off that was used for the analysis.

Conﬁdential/Proprietary Information -83- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al.

CCA (Day 1, CV Score=0.68) CCA (Day 2, CV Score=0.31) 1.0 1.0 0.8 0.8 0.6 0.6 0.4 0.4 Canonical Correlation Canonical Correlation 0.2 0.2 0.0 0.0 1 2 3 4 5 1 2 3 4 5 Canonical Correlation Component Canonical Correlation Component

CCA (Day 7, CV Score=0.14) CCA (Day 14, CV Score=0.27) 1.0 1.0 0.8 0.8 0.6 0.6 0.4 0.4 Canonical Correlation Canonical Correlation 0.2 0.2 0.0 0.0 1 2 3 4 5 1 2 3 4 5 Canonical Correlation Component Canonical Correlation Component

Figure 8: Canonical correlation scree plots for combined study groups. CV-score represents cross validation score.

4 References

[1] Mulligan, Mark J., et al. "Tularemia vaccine: Safety, reactogenicity,"’Take"’ skin reactions, and an- tibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain-A phase 2 randomized clinical Trial." Vaccine 35.36 (2017): 4730-4737.

[2] Johnson, W. Evan, Cheng Li, and Ariel Rabinovic. "Adjusting batch effects in microarray expression

Conﬁdential/Proprietary Information -84- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. data using empirical Bayes methods." Biostatistics 8.1 (2007): 118-127.

[3] Subramanian, Aravind, et al. "Gene set enrichment analysis: a knowledge-based approach for in- terpreting genome-wide expression proﬁles." Proceedings of the National Academy of Sciences 102.43 (2005): 15545-15550.

[4] Kanehisa, Minoru, and Susumu Goto. "KEGG: kyoto encyclopedia of genes and genomes." Nucleic acids research 28.1 (2000): 27-30.

[5] Liberzon, Arthur, et al. "Molecular signatures database (MSigDB) 3.0." Bioinformatics 27.12 (2011): 1739-1740.

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