Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses

INTRODUCTION: Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid (TT) vaccine responses. METHODS: We evaluated gut microbiota by 16S rRNA gene sequencing in 278 South African and Nigerian infants during the first and at 15 weeks of life and measured antibodies against TT vaccine by enzyme-linked immunosorbent assay (ELISA) at matched time points. RESULTS: Infant gut microbiota and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among EBF South African infants. Lasso regression suggested that HIV exposure and gut microbiota were independently associated with TT vaccine responses at week 15, and that high passive antibody levels may mitigate these effects. CONCLUSION: In two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and country, but both specific gut microbes and HIV exposure independently predicted humoral vaccine responses.