Grant: Operating Grant - PA: Bridge Funding -CHVI Vaccine Discovery and Social Research

The human intestine is colonized with microbes (bacteria) during birth and through dietary exposure. Collectively, the bacterial cells (microbiota) help with the uptake of dietary nutrients, develop and maintain immune functions and defend against invading pathogens (germs). The composition of the intestinal bacteria differs between individuals and is highly variable in the first year of life. Of interest, factors in breast milk are known to support protective microbiota and premature weaning is known to change the infant's intestinal microbiome. Alterations in the commensal bacterial composition of the intestine may explain why babies born to HIV+ women who are exclusively breastfed are less likely to get infected with the virus than babies who receive both breast milk and non-sterile food supplements. Disturbances in intestinal bacteria may also explain the reduced efficacy of some childhood vaccinations in developing countries. Under the proposed research, we will apply advanced analytic tools to determine the genetic microbial composition of the intestine of infants currently enrolled in a large African cohort of 600 HIV+ and 100 HIV-negative mother-infant pairs, that is designed to explore the effect of different feeding practices on immune system activation and vaccine responsiveness among breastfed versus mixed fed infants. The bacterial composition and diversity of the intestine will be associated with different feeding practices, vaccine responses, infant immune activation and disease susceptibility. Additionally, microbes in the saliva will be associated with the intestinal microbiome and the immune factors. Overall, this study will aim to identify characteristics of the infant intestinal microbiome that are essential for optimal immune system development, in order to prevent breast milk HIV transmission and optimize infant vaccination strategies.