Summary: 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. A second critical contributor to diseases and many physiological parameters in humans is the microbiome. The intestinal microbiome has been shown to be related to a broad range of human diseases including many viral and metabolic diseases. Despite this emerging recognition that the microbiome has profound effects on immune and inflammatory processes in mammals, the effects of the microbiome on vaccine responses are less well defined. Our major hypothesis is that parasitic infection will alter the HepB vaccine response by modifying the state of the innate immune system and microbiome complexity, thereby qualitatively compromising the de novo priming of vaccine-induced T cell and B cell immunity. Our objective is to integrate and develop immune models of the molecular and sub-network signatures that characterize host response to HepB vaccination from low to high helminth burden, by using innovative bioinformatics and systems biology analyses.