Abstract
Objective: The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty).
Design: We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA.
Results: We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05).
Conclusion: Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.
Keywords: COVID-19; enteric bacterial microflora; immune response.
【저자키워드】 COVID-19, immune response, enteric bacterial microflora, 【초록키워드】 SARS-CoV-2, Vaccine, BNT162b2 vaccine, immune response, vaccination, Anti-inflammatory, antibody, mRNA vaccine, CoronaVac, Intervention, complement, metabolism, BNT162b2, Stool, COVID-19 vaccines, Virus neutralisation, Host immune response, Inactivated vaccine, adverse event, Microbiome, Effectiveness, pathway, Bacteria, gut microbiota, spike receptor-binding domain, IgG ELISA, metagenomic sequencing, Sinovac, Bacterial, association, marker, Prevotella, Gut, subject, second dose, individual, positive correlation, carbohydrate, vaccinees, recipient, flagella, gut microbiota composition, significantly lower, Linear Discriminant Analysis, vaccinee, Bifidobacterium, performed, collected, conducted, reduced, the vaccine, were measured, baseline, COVID-19 vaccinee, high neutralising antibody, modulating, 【제목키워드】 SARS-CoV-2 vaccine, microbiota, adverse event,