IMPACT OF GUT MICROBIOTA ON VACCINE RESPONSE IN HIV EXPOSED INFANTS

Abstract

Abstract Maternal HIV infection has been shown to alter the composition and diversity of gut microbiota in their infants. We hypothesized that inheritance of an altered microbiota in HIV-exposed uninfected (HEU) infants is associated with poor vaccine responses. Here, using a germ free mouse model, we investigate the causative relationship between stool microbiota in HEU infants and BCG vaccine response. BCG vaccine Th1 responses were assessed using a whole blood assay and an intracellular cytokine flow cytometry panel. Stool samples from time of BCG vaccination were collected, and those from high or low BCG responder infants transferred by oral gavage to germ free pups at day 5 after delivery. Five days after gavage, pups were sacrificed to analyze inherent immunity or vaccinated with 10^6 CFUs of BCG. Vaccinated animals were sacrificed 28 days post vaccination. BCG specific T cells were quantified using TB10.4 (class I) tetramers by flow cytometry. At d10 post-delivery, pups gavaged with high responder stool (Phr) had significantly lower spleen cell count compared to those gavaged with low responder stool (Plr). Furthermore, Phr pups had significantly higher proportions but not numbers of effector memory CD4 T cells (CD4+CD44hiCD62Llo) relative to Plr. Total number of B cells and neutrophils were significantly reduced in Phr vs Plr. When vaccinated with BCG, Phr displayed significantly higher number of TB10.4-specific CD8 T cells compared to Plr. Our data shows a direct role of the microbiota in inherent immunity in infants. Furthermore, the microbiota in low responder HEU infants caused reduced number of vaccine specific CD8 T cells. Together, we show for the first time that intestinal microbiota in human infants at birth impacts vaccine response.