Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV

The mRNA-based SARS-CoV-2 vaccines are safe with clinical efficacy against COVID-19. Recent studies have focused on exploring variation of immune responses to SARS-CoV-2 vaccines in the general population. As the gut microbiome is factor known to influence vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immune responses to the BNT162b2 mRNA SARS-CoV-2 vaccine in healthy controls (HC) and people living with HIV (PLWH) who received two doses of BNT162b2.16S rRNA sequencing was performed on DNA extracted from fecal samples collected from PLWH and HC prior to vaccination. Humoral and cellular responses to the SARS-CoV-2 vaccine were evaluated on day 35 after the first dose.Bifidobacterium and Faecalibacterium were identified as markers of high responders to the SARS-CoV-2 BNT162b2 mRNA vaccine and Cloacibacillus in low responders, irrespective of other clinical parameters.Our results show strong associations between microbial diversity and spike IgG responses after BNT162b2 vaccination, both in PLWH and HC. These findings were consistent in the whole cohort, albeit group differences in microbial diversity and composition between HC and PLWH were observed. We propose that microbiome modulation could optimize immunogenicity of SARS-CoV-2 mRNA vaccines.