The microbiome is a key contributor to many physiologic parameters and diseases in mammals, but the effects on vaccine responses are less well defined. The microbiome has co-evolved with mammals over millions of years to include an estimated 100 trillion bacteria and perhaps 10-fold more viruses. We have recently found that anaerobic bacteria have profound effects on the generation of IL10-expressing CD4 Treg cells through autophagy gene-dependent mechanisms in both mice and humans. Importantly, it has been shown that preexisting antibodies to enteric bacteria can skew vaccine responses to cross-reacting HIV-1 antigen, arguably rendering a vaccine less protective and that enteric bacterial components regulate the vaccine response to influenza in mice through activation of Toll-like receptors. Helminth infections also have profound effects on host immune response. Limited study in human suggests that helminth infection may alter bacterial microbiome61. Helminths are documented to lower the efficacy of vaccination. The role of Core C is to provide centralized computational and technologic expertise, sequencing, and algorithms to generate an in depth analysis of the microbiome in subjects within the study cohorts that will be critical to understand both difference in the microbiome between subjects with and without helminth infection and the relationship between these descriptors and vaccine responses. Integrated analysis linking variations in the microbiome to study cohort metadata including measures of immune responses and other '-omic' signatures may lead to identification of digital and molecular signatures within the microbiome and host baseline immune characteristics that may be predictive of vaccine efficacy. Should the hypothesis of the U19 grant be validated (that the microbiome correlates with changes in basal immune parameters and vaccine responses), we will identify computational models that can be used as a component of analyses of new vaccines; these will be made accessible to the broader research community.
The microbiome has profound effects on normal physiology and disease, in particular as relates to the immune system and may therefore influences vaccine responses. Core C will provide quantitative analysis of all components of the fecal microbiome in samples from study cohorts to support that Aims of individual U19 projects.
