Gut microbiota composition modulates SARS-CoV-2 vaccine immunogenicity and vaccine-related adverse effects

Vaccines targeting SAR-CoV-2 are effective in preventing COVID-19 but plasma neutralizing activity varies between individuals and amongst vaccines. The gut microbiota has emerged as a key factor in modulating immune responses to vaccination. Here we examined gut microbiota composition and antibody response in a cohort of SARS-CoV-2 naive individuals who had received two doses of BNT162b2, an mRNA-based vaccine (Comirnaty; Fosun-BioNTech) or Corovac, an inactivated virus (vero cell) vaccine (Coronava; Sinovac). Plasma neutralization and levels of binding IgG after second vaccine dose were higher in subjects with mRNA than inactivated vaccines. A higher relative abundance of bacteria with flagellin including Roseburia faecis was associated with a higher antibody response to mRNA vaccine. Bifidobacterium adolescentis was persistently higher in responders than low-responders to inactivated vaccine. Responders also had higher abundances of pathways related to carbohydrate metabolism and pathways that positively correlated with abundance of Bifidobacterium adolescentis. The abundance of Prevotella copri and two Megamonas species were enriched in participants with less adverse effects following mRNA and inactivated vaccines indicating that these bacteria species may play an anti-inflammatory role in host immune response. Thus, antibody and neutralization levels were associated with distinct gut microbiota composition following vaccination. These results suggest that boosting vaccinated individuals with specific bacteria species may not only prime the immune system to mount a more potent response after COVID-19 vaccination but also potentially minimize vaccine-related adverse effects.