Baseline Gut Microbiota Was Associated with Long-Term Immune Response at One Year Following Three Doses of BNT162b2

• Published in: Vaccines (Basel) Vol. 12; no. 8; p. 916
• Main Authors: Zhang, Li-Na, Tan, Jing-Tong, Ng, Ho-Yu, Liao, Yun-Shi, Zhang, Rui-Qi, Chan, Kwok-Hung, Hung, Ivan Fan-Ngai, Lam, Tommy Tsan-Yuk, Cheung, Ka-Shing
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 14.08.2024; MDPI
• Subjects: Antibiotics; Antibodies; Antigens; Bacteria; Biosynthesis; Blood levels; COVID-19; COVID-19 vaccines; Discriminant analysis; Disease transmission; DNA sequencing; Enzyme-linked immunosorbent assay; Feces; gastrointestinal microbiome; Gene sequencing; Histidine; IgG antibody; Immune response; Immune system; Immunogenicity; Immunoglobulin G; Immunoglobulins; Infections; Intestinal microflora; Metabolic pathways; Metabolism; Metabolites; Metagenomics; Microbiota; Microorganisms; Mortality; Neutralizing; Probiotics; Pyrimidines; Relative abundance; Ribonucleotides; Severe acute respiratory syndrome coronavirus 2; Shotguns; Statistical analysis; Swine flu; Vaccination; vaccine; United States > US; Germany
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines12080916

Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2. Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis. Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2–59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log10LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10−5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log10LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log10LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log10LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log10LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10−5% vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log10LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log10LDA score = 2.14). Conclusion: Among three-dose BNT162b2 recipients, S. parasanguinis, B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.