Baseline Gut Microbiome Signatures Correlate with Immunogenicity of SARS-CoV-2 mRNA Vaccines

Abstract

The powerful immune responses elicited by the mRNA vaccines targeting the SARS-CoV-2 Spike protein contribute to their high efficacy. Yet, their efficacy can vary greatly between individuals. For vaccines not based on mRNA, cumulative evidence suggests that differences in the composition of the gut microbiome, which impact vaccine immunogenicity, are some of the factors that contribute to variations in efficacy. However, it is unclear if the microbiome impacts the novel mode of immunogenicity of the SARS-CoV-2 mRNA vaccines. We conducted a prospective longitudinal cohort study of individuals receiving SARS-CoV-2 mRNA vaccines where we measured levels of anti-Spike IgG and characterized microbiome composition, at pre-vaccination (baseline), and one week following the first and second immunizations. While we found that microbial diversity at all timepoints correlated with final IgG levels, only at baseline did microbial composition and predicted function correlate with vaccine immunogenicity. Specifically, the phylum Desulfobacterota and genus Bilophila, producers of immunostimulatory LPS, positively correlated with IgG, while Bacteroides was negatively correlated. KEGG predicted pathways relating to SCFA metabolism and sulfur metabolism, as well as structural components such as flagellin and capsular polysaccharides, also positively correlated with IgG levels. Consistent with these findings, depleting the microbiome with antibiotics reduced the immunogenicity of the BNT162b2 vaccine in mice. These findings suggest that gut microbiome composition impacts the immunogenicity of the SARS-CoV-2 mRNA vaccines.

Investigation of Gut Microbiota Disorders in Sepsis and Sepsis Complicated with Acute Gastrointestinal Injury Based on 16S rRNA Genes Illumina Sequencing

“…The Desulfobacterota can synthesize immunostimulatory endotoxin, its play a role in regulating SARS-CoV-2 mRNA vaccines immunogenicity. 36 In this study, the abundance of Desulfobacterota in the sepsis group was increased compared to the control group. This suggested that the Desulfobacterota abundance anomalies may be associated with the occurrence of sepsis.…”

Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective

“…The gut microbiota influences the immunogenicity of the COVID-19 mRNA vaccines. A prospective cohort study found a positive correlation between pre-vaccination microbial diversity and composition (e.g., the phylum Desulfobacterota and genus Bilophila , synthesizing immunostimulatory endotoxin) and the final levels of anti-spike IgG [ 117 ]. Moreover, the antibiotic-induced depletion of the gut microbiome in mice was observed to reduce the immunogenicity of the Pfizer (BNT162b2) vaccine [ 117 ].…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…These results confirm that the gut microbiota composition influences the immunogenicity of SARS‐CoV‐2 mRNA vaccines. 179 The role of the gut microbiome in modulating the durability of immunity against COVID‐19 vaccines remains unclear. Gut microbiota sequencing and blood analysis at baseline, 1 month, and 6 months after vaccination revealed that multiple inflammatory factors, chemokines, and antibodies were associated with gut microbiota and metabolites, and that the abundance of some microbiota was associated with higher antibody levels at 6 months, suggesting that microbiota adjuvants may prolong the durability of the immune response to the SARS‐CoV‐2 vaccine.…”