Investigating the impact of helminth infection on microbioma composition and innate immunity generated during HepB vaccination.

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Abstract In parts of Africa, there is a heavy burden of parasitic diseases, including intestinal worms of several genera, collectively called helminths, and malaria. Some recent studies have implicated the worms in particular, in biasing the immune response towards a Th2 phenotype resulting in alteration of T cell and B cell responses. In fact recent work in mice has shown that pre-existing infection with Schistosoma mansoni down-regulates anti- HepB antibody levels and reduces response to vaccine, and multiple reports have indicated that helminthic infections may be a contributing cause for weak responsiveness to the vaccines. However, very little information is available on the influence of parasites in general or helminth in particular on host immune response to vaccines in humans. Thus an objective and comprehensive survey of the impact of parasitic infection on vaccine induced immunity may point to potential interventional immunologic targets that may target a critical unmet need, enabling the development of vaccines for the developing world. Our major hypothesis is that single or multiple parasites will modify the differentiation and priming of T cells following HepB vaccination leading to diminished antigen-specific memory and effector T cell responses. We will perform experiments in aim 1 to assess the phenotype and function of antigen-specific T cells. In aim 2 we will determine whether infection with single or multiple parasites will affect the priming of CD4+ T cells and aim 3 we will determine whether infection with helminth will influence CD4+ T cell differentiation programs and programing of follicular helper T cells (Tfh) cells. The ultimate objective is to develop digital and molecular signatures of immune response to HepB vaccine in the context of co-infection with endemic parasitic infections including Schistosoma, soil-transmitted helminths and malaria.