Mechanisms of differential responses to whole cell and acellular pertussis vaccination

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PROJECT SUMMARY Overall Component Vaccines are one of the most cost effective and extraordinarily successful medical interventions. Most of those vaccines depend on CD4 T+ cells and their help to B cells. Our understanding of in vivo, specific human CD4+ T cell responses to pathogens remains hazy, due to the complexity of the biology, the rarity of the cells, relatively inaccessible tissue localization, and technical challenges of identifying specific CD4+ T cells. Therefore, our approach to this serious problem has been to develop multiple new techniques to study human CD4+ T cells over the past several years. While CD4+ T cell-dependent antibody responses have been the source of protection for most licensed vaccines (Project 1), there is a very good argument to be made that many of the diseases for which we do not have successful vaccines require adaptive immune responses beyond antibodies for protection (Projects 2 and 3). The three Projects proposed here vigorously pursue an understanding of the mechanisms regulating human anti-pathogen CD4+ T cells, linked by new experimental approaches.