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Transcriptome Analysis of Vaccine Responses to Francisella Tularensis Or Venezuelan Equine Encephalitis Virus Rebecca Ann Erwin-Cohen Walden University

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Transcriptome Analysis of Vaccine Responses to Francisella Tularensis Or Venezuelan Equine Encephalitis Virus Rebecca Ann Erwin-Cohen Walden University Walden University ScholarWorks Walden Dissertations and Doctoral Studies Walden Dissertations and Doctoral Studies Collection 2016 Transcriptome Analysis of Vaccine Responses to Francisella Tularensis or Venezuelan Equine Encephalitis Virus Rebecca Ann Erwin-Cohen Walden University Follow this and additional works at: https://scholarworks.waldenu.edu/dissertations Part of the Epidemiology Commons, Public Health Education and Promotion Commons, and the Systems Biology Commons This Dissertation is brought to you for free and open access by the Walden Dissertations and Doctoral Studies Collection at ScholarWorks. It has been accepted for inclusion in Walden Dissertations and Doctoral Studies by an authorized administrator of ScholarWorks. For more information, please contact [email protected]. Walden University College of Health Sciences This is to certify that the doctoral dissertation by Rebecca Ann Erwin-Cohen has been found to be complete and satisfactory in all respects, and that any and all revisions required by the review committee have been made. Review Committee Dr. Ji Shen, Committee Chairperson, Public Health Faculty Dr. Bin Cai, Committee Member, Public Health Faculty Dr. James Rohrer, University Reviewer, Public Health Faculty Chief Academic Officer Eric Riedel, Ph.D. Walden University 2016 Abstract Transcriptome Analysis of Vaccine Responses to Francisella Tularensis or Venezuelan Equine Encephalitis Virus by Rebecca A. Erwin-Cohen MS, Hood College, 1995 BS, Gannon University, 1990 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Public Health -- Epidemiology Walden University December 2016 Abstract The lack of vaccines for emerging and re-emerging diseases highlights technical gaps and indicates a need for innovative approaches to produce new vaccines. Vaccines may be improved by knowledge of host responses to vaccination, disease pathogenesis, and the effect of age and genetics on vaccine outcome. This study’s purpose was to quantitatively assess the molecular epidemiology of Francisella tularensis (Ft) and Venezuelan Equine Encephalitis Virus (VEEV). Study results support the Epidemiology Nexus model which holds that association of changes in gene expression to vaccination facilitate understanding the mechanisms of immune development and link public health and disease epidemiology. My research questions assessed the relationship between gene expression following vaccination, the relationship between age and vaccine response, and the association between Human Leukocyte Antigen (HLA) allele and vaccine response. The study was a novel secondary analysis of human data subjected to ANOVA to measure association between treatment and outcome, correlation to measure association of age with vaccine outcome, and Mann-Whitney U tests to measure association of HLA allele with vaccine outcome. Both Ft and VEEV vaccination elicited significant changes in gene expression. A highly positive relationship between age and vaccine outcome was shown for VEEV. The results may affect positive social change by contributing to a growing compendium of evidence of vaccine efficacy mechanisms that may function to assure the public of vaccine safety, combat vaccine hesitancy, and promote vaccine acceptance, as well as contribute mechanistic knowledge to reduce developmental costs of novel vaccines. Transcriptome Analysis of Vaccine Responses to Francisella Tularensis or Venezuelan Equine Encephalitis Virus by Rebecca A. Erwin-Cohen MS, Hood College, 1995 BS, Gannon University, 1990 Dissertation Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Public Health - Epidemiology Walden University December 2016 Dedication I dedicate this work to my family; my beloved husband, Jeffrey, and our wonderful daughter, Aislinn. Their love, support, and encouragement made it possible to begin this scholarly journey and to see it through to the conclusion. I am grateful for the love and companionship of Daisy, Sookie, Walter, and BabbaLooey. I am also grateful for the encouragement and support of many friends, family, and colleagues, who excused my absences and absent-mindedness, lifted my spirits when down, and at the end of it all still want to spend time with me. Thank you all for supporting me. Acknowledgments I will be eternally grateful for the support and guidance of my committee. I would like to express my sincere thanks and gratitude to Dr. Ji Shen for his patience, wisdom, and guidance throughout the process of writing this dissertation; Dr. Bin Cai for his guidance on statistical analyses and interpretations; and Dr. James Rohrer for guidance and a keen eye for adhering to the guidelines and expectations of Walden. I would like to thank Dr. Luis DaSilva for his mentoring, for teaching me transcriptome analysis, and for being one of the finest human beings I’ve ever had the good fortune to meet. Finally, I would like to thank COL Shelley Honnold for her mentoring, encouragement, critical review of chapters, and friendship. The complete dissertation has been cleared for public presentation and dissemination under USAMRIID approval PR-17-009. The following human use protocols were associated with the work described herein: FY-05-01, FY-06-17. USAMRIID work has been funded through Department of Defense grant #05-4-8I-052 and Defense Threat Reduction Agency grant # 8.10022_05_RD_B. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U.S. Army. Table of Contents List of Tables ..................................................................................................................... vi List of Figures .................................................................................................................. viii Chapter 1: Introduction to the Study ....................................................................................1 Introduction ....................................................................................................................1 Background ....................................................................................................................3 General Overview of Francisella Tularensis ......................................................... 4 General Overview of Venezuelan Equine Encephalitis Virus .............................. 10 Problem Statement .......................................................................................................15 Study Purpose ..............................................................................................................18 Research Questions and Hypotheses ...........................................................................19 Research Question 1 ............................................................................................. 19 Research Question 2 ............................................................................................. 19 Research Question 3 ............................................................................................. 20 Research Question 4 ............................................................................................. 20 Conceptual Framework ................................................................................................21 Nature of the Study ......................................................................................................22 Definitions....................................................................................................................24 Assumptions .................................................................................................................26 Scope and Delimitations. .............................................................................................26 Limitations ...................................................................................................................27 Significance..................................................................................................................28 i Summary ......................................................................................................................30 Chapter 2: Literature Review .............................................................................................32 Problem Addressed by the Study .................................................................................32 Purpose of the Study ....................................................................................................32 Literature Relevant to the Problem ..............................................................................33 Literature Search Strategy............................................................................................34 Conceptual Framework ................................................................................................35 Theoretical Concepts ............................................................................................ 35 How the Current Study May Benefit From the Epidemiology Nexus Concept ..................................................................................................... 42 Literature Review Related to Key Variables and Concepts .........................................44 Previous Transcriptomic Studies of Human Responses to Ft or VEEV: Relation to Key Study Variables............................................................... 44 Strengths and
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