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

Abstract

<p> <span>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. </span><em>Streptococcus parasanguinis</em><span> (log</span>₁₀<span>LDA score = 2.38, </span><em>p</em><span> = 0.003; relative abundance of 2.97 × 10</span>⁻⁵<span> vs. 0.03%, </span><em>p</em><span> = 0.001), </span><em>Bacteroides stercoris</em><span> (log</span>₁₀<span>LDA score = 4.29, </span><em>p</em><span> = 0.024; relative abundance of 0.14% vs. 2.40%, </span><em>p</em><span> = 0.014) and </span><em>Haemophilus parainfluenzae</em><span> (log</span>₁₀<span>LDA score = 2.15, </span><em>p</em><span> = 0.022; relative abundance of 0.01% vs. 0, </span><em>p</em><span> = 0.010) were enriched in low responders. </span><em>Bifidobacterium pseudocatenulatum</em><span> (log</span>₁₀<span>LDA score = 2.99, </span><em>p</em><span> = 0.048; relative abundance of 0.09% vs. 0.36%, </span><em>p</em><span> = 0.049) and </span><em>Clostridium leptum</em><span> (log</span>₁₀<span>LDA score = 2.38, </span><em>p</em><span> = 0.014; relative abundance of 1.2 × 10</span>⁻⁵<span>% vs. 0, </span><em>p</em><span> = 0.044) were enriched in high responders. </span><em>S. parasanguinis</em><span> was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log</span>₁₀<span>LDA score = 2.63), which contributes to inflammation and antibody production. </span><em>H. parainfluenzae</em><span> was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log</span>₁₀<span>LDA score = 2.14). Conclusion: Among three-dose BNT162b2 recipients, </span><em>S. parasanguinis</em><span>, </span><em>B. stercoris</em><span> and </span><em>H. parainfluenzae</em><span> were associated with poorer immunogenicity at one year, while </span><em>B. pseudocatenulatum</em><span> and </span><em>C. leptum</em><span> was associated with a better response.</span> <br></p>