CLINICAL TRIAL: CLONAL B-CELL RESPONSES TO TRIVALENT CLONAL B-CELL RESPONSES TO

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. While influenza vaccines exist, the immunologic mechanisms by which protection is induced in the respiratory tract are poorly understood in the human host. It is well known that the protective efficacy of trivalent inactivated influenza virus (TIV) vaccine in the elderly is inferior compared to that in healthy young adults. The underlying mechanism for the difference is not well understood but is likely to involve differences in the specificity of antibody immune responses following vaccination. It is our hypothesis that TIV vaccination induces a humoral response with greater heterosubtypic diversity in healthy young adults than in the elderly, and that this diversity will be apparent in serum and at a clonal level when studied using monoclonal antibodies derived from young and elderly vaccinees. Induction of such heterosubtypic immunity by vaccination would be advantageous in the event of the emergence in the population of a drift variant influenza strain. A broadly reactive, single human monoclonal antibody (Mab) that reacts efficiently with several drifted influenza strains has not been described and identifying such a molecule would prove that this form of reactivity could contribute to heterosubtypic immunity. Alternatively, isolation of Mabs that demonstrate enhanced reactivity (>4-fold increase) against a heterosubtypic strain versus the homotypic immunizing strain would provide evidence that antibody clonal diversity could also be a potential mechanism to account for heterosubtypic immunity in serum. Analysis of a library of Mabs isolated from the immunized subjects will be done to try to determine whether evidence for either of these two possibilities can be found and if so, which mechanism occurs more frequently. We will also compare the 'trafficking receptor profile" of plasmablasts induced by influenza vaccination.