Associations between the microbiome and immune responses to an adenovirus-based HIV-1 candidate vaccine are distinct between African and US cohorts.

Optimization of prophylactic vaccine regimens to elicit strong, long-lasting immunity is an urgent need highlighted by the COVID-19 pandemic. Stronger vaccine immunogenicity is frequently reported in individuals living in high-income countries compared to individuals living in low- and middle-income countries. While numerous host genetic and immune factors may influence vaccine responses, geographic restrictions to vaccine effectiveness may also be influenced by the intestinal microbiota, which modulates host immune systems. However, the potential role of the gut microbiota on responses to HIV-1 vaccines has not yet been explored. We analyzed the bacteriome by targeted 16S sequencing and the virome by virus-like particle sequencing of 154 fecal samples collected from healthy individuals in Uganda, Rwanda, and the United States early (week 2) and late (week 26) after vaccination with multivalent adenovirus serotype 26 (Ad26)-vectored mosaic HIV-1 vaccines. Vaccination did not affect the enteric bacteriome or virome regardless of geographic location. However, geography was the major driver of microbiota differences within this cohort. Differences in overall bacterial and viral diversity and in specific microbial taxa, including