APPROACH Microbiome

The intestinal microbiota is an important factor that influences the development and regulation of host immune systems. However, the interplay between intestinal microbial populations and systemically administered vaccines has not been well-explored. Here, we analyzed the fecal bacteriome and virome of 154 samples collected early and late in the vaccination time-course from mosaic HIV-1-vaccinated healthy individuals in Uganda, Rwanda, and the US. Geography was the major driver of microbiota differences within our cohort. Our analysis indicates that Ad26-based HIV-1 vaccination does not affect the enteric bacteriome or virome regardless of the geographic location of those vaccinated. However, regional microbial communities and taxa were associated with specific immune responses to Ad26-based HIV-1 vaccines. Thus, while overall safety and efficacy of Ad26-based HIV-1 vaccination is robust across regions, there are strong associations between specific bacterial taxa and individual components of HIV-1 vaccine responses.