Innate, Adaptive, and Mucosal Immune Responses in HIV-1 Exposed Uninfected Infants: A Human Model to Understand Correlates of Immune Protection

The transmission of HIV from an infected mother to her infant via breastfeeding is remarkably inefficient. Despite repeated exposure to HIV in the breast milk, the majority of infants who are exclusively breastfed (EBF) do not become infected. Interestingly, infants that are EBF are less likely to be infected by their HIV+ mothers compared to infants who receive other sources of liquid or food in addition to breast milk, despite consuming more HIV infected milk. To better understand this unusual finding, our research aims to identify factors in breast milk that protect infants from HIV infection and/or inflammatory responses of the infant gut following different feeding practices that may increase susceptibility to HIV infection. Our program of work also proposes to examine the effect of previous immune activation in the infant on immune responses to standard childhood vaccinations and to evaluate maternal attitudes and beliefs about breastfeeding and their willingness to enroll their infants in future HIV vaccine trials. We have assembled a strong, international multi-discipinary team of investigators to carry out these studies in Nigeria and South Africa, countries with the highest number of HIV+ pregnant women. Understanding modes of natural protection as well as immune activation in the HIV exposed but uninfected infant provides critical information to HIV vaccine development and especially testing in developing countries with high HIV prevalence.