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

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Systems Vaccinology for a Live Attenuated Tularemia Vaccine Reveals Unique Transcriptional Signatures That Predict Humoral and Cellular Immune Responses 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 inten- sity fold change from baseline by treatment. 20 Table 24 Descriptive summary statistics of monocyte cells (CD16- CD86-) mean fluorescence inten- sity 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 in- tensity fold change from baseline by treatment. 21 Table 27 Descriptive summary statistics of monocyte cells (CD16- CCR5-) mean fluorescence inten- sity 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 fluores- cence 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 fluores- cence 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 flu- orescence intensity fold change from baseline by treatment. 23 Table 38 Descriptive summary statistics of natural killer cells (CD56 dim CD16- CD69-) mean fluo- rescence 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 in- tensity fold change from baseline by treatment. 24 Confidential/Proprietary Information -3- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Table 42 Descriptive summary statistics of monocyte cells (CD16- HLA-DR) mean fluorescence in- tensity 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 base- line by treatment. 25 Table 47 Descriptive summary statistics of Human Interleukin-4 concentration fold change from base- line by treatment. 25 Table 48 Descriptive summary statistics of Human Interleukin-5 concentration fold change from base- line by treatment. 25 Table 49 Descriptive summary statistics of Human Interleukin-6 concentration fold change from base- line by treatment. 25 Table 50 Descriptive summary statistics of Human Interleukin-7 concentration fold change from base- line by treatment. 25 Table 51 Descriptive summary statistics of Human Interleukin-8 concentration fold change from base- line by treatment. 26 Table 52 Descriptive summary statistics of Human Interleukin-9 concentration fold change from base- line 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 concentra- tion 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 Confidential/Proprietary Information -4- Supp. Text "‘Transcriptomics of tularemia vaccines"’ Natrajan et al. Table 63 Descriptive summary statistics of Human Interferon gamma-induced protein.
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