Despite our growing tool kit of clinically approved vaccines that prevent millions of lives annually, vaccine effectiveness is not equivalent across the globe, with particularly low coverage rates in the developing world. Among the potential contributors to vaccine failures in the developing world, accessibility, cold chain breaks, and education have been implicated as structural barriers to vaccine effectiveness. However, emerging evidence both in humans and animal models point to a critical role of parasitic infections as immunological confounders of vaccine induced immunity. Specifically, parasites infect more than a third of the world and have evolved over millennia to co-exist with their hosts. To achieve co-existence, parasites have evolved immunosuppressive strategies that dramatically alter the host?s immune system. These alterations include enhanced anti-inflammatory cytokine expression profiles and skewed T-helper (Th) immunity that collectively have been implicated in impaired response to both de novo infections and vaccination. However, the impact of parasitic infections on altered antibody immunity has been more controversial, where parasitic infection has been linked to reduced overall antibody titers in some vaccines but not others. However, given the critical role of Th immunity in programming the humoral response, it is plausible that while parasitic infection may only alter the overall magnitude of the humoral immune response variably, that these immunologic changes may have a dramatic impact on shaping the quality of the humoral immune response. Thus under this project we aim to comprehensively dissect the impact of parasitic co-infection on altering and shaping both the state of the vaccine induced memory B cell response as well as the functional character of the vaccine induced antibodies.
