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Association between Gut Microbiota Composition and Long-Term Vaccine Immunogenicity following Three Doses of CoronaVac
oleh: Li-Na Zhang, Jing-Tong Tan, Ho-Yu Ng, Yun-Shi Liao, Rui-Qi Zhang, Kwok-Hung Chan, Ivan Fan-Ngai Hung, Tommy Tsan-Yuk Lam, Ka-Shing Cheung
Format: | Article |
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Diterbitkan: | MDPI AG 2024-03-01 |
Deskripsi
Background: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac. Methods: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors. Results: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9–56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. <i>Eubacterium rectale</i> (log<sub>10</sub>LDA score = 4.15, <i>p</i> = 0.001; relative abundance of 1.4% vs. 0, <i>p</i> = 0.002), <i>Collinsella aerofaciens</i> (log<sub>10</sub>LDA score = 3.31, <i>p</i> = 0.037; 0.39% vs. 0.18%, <i>p</i> = 0.038), and <i>Streptococcus salivarius</i> (log<sub>10</sub>LDA score = 2.79, <i>p</i> = 0.021; 0.05% vs. 0.02%, <i>p</i> = 0.022) were enriched in low responders. The aOR of high immune response with <i>E. rectale, C. aerofaciens</i>, and <i>S. salivarius</i> was 0.03 (95% CI: 9.56 × 10<sup>−4</sup>–0.32), 0.03 (95% CI: 4.47 × 10<sup>−4</sup>–0.59), and 10.19 (95% CI: 0.81–323.88), respectively. <i>S. salivarius</i> had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log<sub>10</sub>LDA score = 2.23). <i>C. aerofaciens</i> similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions. Conclusion: <i>E. rectale,</i><i>C. aerofaciens</i>, and <i>S. salivarius</i> correlated with poorer long-term immunogenicity following three doses of CoronaVac.