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Abstract
Vaccination is one of the most cost-effective preventive measures for many infectious diseases, including influenza. However, the constant-evolving nature of influenza A virus (IAV) leads to annual revision of seasonal influenza vaccine components and at times, antigenic mismatch can potentially occur with the vaccine target, hemagglutinin (HA). In the case of swine, vaccines in use may not protect against the viruses that spread in pigs as there is no formal vaccine strain recommendation system and variation in swine influenza strains may arise. Human and swine influenza studies have shown that when vaccine strain and circulating strains are poorly matched, highly conserved T cell epitopes may limit disease spread in the absence of cross-reactive antibodies. Despite these findings, most influenza vaccine studies focus on humoral immune mechanisms and means of measuring the correlates of protection for T cell epitopes are still lacking. This dissertation addresses knowledge gaps in the vaccine development from the cellular-mediated immunity perspective. The goal of this dissertation is to evaluate T cell epitope conservation in influenza vaccines against circulating IAV viruses in swine and humans using T cell epitope prediction algorithms and phylogenetic analysis tools. Research aim 1 focuses on assessing a conserved T cell epitope-based prototype vaccine and determining the persistence of T cell epitope conservation over a 5-year period. Aim 2 concentrates on identifying cross-conserved T cell epitope in HA sequences of human and swine influenza vaccines against emergent H1N1 G4 swine IAV (G4) to evaluate the potential for the G4 strain to impact swine and human populations. The work in aim 3 is about defining the human T cell immune landscape of H3N2 IAV using HA sequence data to estimate potential T cell epitopes and to examine how antigenic drift affects the diversity of T cell epitopes presented by the viral population over time. Collectively, my research findings present rationale for the use of computational means to analyze high dimensional data in the study of host immunity related to infection or vaccination by influenza virus. The studies outcomes also provide useful insights that may enhance influenza vaccine strategies as well as influenza surveillance efforts.