Adaptive immunity plays a critical role in eradicating viral infections. This project aims to study in vivo mechanisms of virus - host interactions and to better understand what constitutes effective primary and memory B- and T-cell responses to virus infection. One component of these studies examines the role of partial or incomplete immunity. Due to the constant antigenic evolution of influenza A viruses (IAV), the specificity of existing anti-virus immunity in the population is typically at best only partially cross-reactive for the infecting virus. Uncertainties about future circulating strains further results in partial immunity through the use of best guess strain specific annual vaccines that are not perfect matches. The existence of partial B-cell and CD8+ T cell immunity raises several important questions including: Are all immunodominant B and T cell specificities equally effective at protecting against infection? Can partial immunity result in the amplification of ineffective immunodominant responses at the expense of more effective specificities? Does partial immunity enhance virus evolution? A second component of these studies aims to better understand and predict the best effector functions required for a protective anti-viral memory response. Specifically, can the most effective specificities and functional features of T and B cell responses be defined and how can these be optimally induced as the immunodominant responses through vaccination. These basic studies are needed to improve the rational design of vaccines and interventions against influenza virus infection. They are important to understanding what can generate the most effective vaccination against IAVs and the potential impact that vaccination may have on viral pathogenesis.
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