Journal Article Epublish 3 citations
PubMed: 40083550 DOI: 10.3389/fimmu.2025.1534787
Gut microbiota is associated with persistence of longer-term BNT162b2 vaccine immunogenicity.
Front Immunol 16:1534787
Authors: Ho Yu Ng, Yunshi Liao, Ching Lung Cheung, Ruiqi Zhang, Kwok Hung Chan, Wai-Kay Seto, Wai K Leung, Ivan F N Hung, Tommy T Y Lam, Ka Shing Cheung
Affiliations
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
- State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
- Department of Pharmacology and Pharmacy, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China. Laboratory of Data Discovery for Health Limited, 19W Hong Kong Science & Technology Parks, Hong Kong, Hong Kong SAR, China.
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China.
- Department of Microbiology, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China.
- State Key Laboratory of Emerging Infectious Diseases, School of Public Health, The University of Hong Kong, Hong Kong, Hong Kong SAR, China. Laboratory of Data Discovery for Health Limited, 19W Hong Kong Science & Technology Parks, Hong Kong, Hong Kong SAR, China. Centre for Immunology & Infection Limited, 17W Hong Kong Science & Technology Parks, Hong Kong, Hong Kong SAR, China.
Abstract
Introduction
BNT162b2 immunogenicity wanes with time and we investigated association between gut microbiota and longer-term immunogenicity.
Methods
This cohort study prospectively recruited adult BNT162b2 two-dose recipients from three vaccination centers in Hong Kong. Blood samples were collected at baseline and day 180 after first dose, and tested for neutralizing antibodies (NAb) against receptor-binding domain (RBD) of wild type SARS-CoV-2 virus using chemiluminescence immunoassay. Shotgun DNA metagenomic sequencing was performed to characterize baseline stool microbiome. Baseline metabolites were measured by gas and liquid chromatography-tandem mass spectrometry (GC-MS/MS and LC-MS/MS). Primary outcome was persistent high NAb response (defined as top 25% of NAb level) at day 180. Putative bacterial species and metabolic pathways were identified using linear discriminant analysis [LDA] effect size analysis. Multivariable logistic regression adjusting for clinical factors was used to derive adjusted odds ratio (aOR) of outcome with bacterial species and metabolites.
Results
Of 242 subjects (median age: 50.2 years [IQR:42.5-55.6]; male:85 [35.1%]), 61 (25.2%) were high-responders while 33 (13.6%) were extreme-high responders (defined as NAb≥200AU/mL). None had COVID-19 at end of study. (logLDA score=3.65), (score=2.82) and (score=2.31) were enriched in high-responders, while was enriched in low-responders (score=-3.70). On multivariable analysis, bacterial species (-aOR: 1.87, 95% CI: 1.02-3.51; -aOR: 2.2, 95% CI: 1.18-4.18; S. -aOR: 2.09, 95% CI: 1.13-3.94) but not clinical factors associated with high response. positively correlated with most metabolic pathways enriched in high-responders, including superpathway of L-cysteine biosynthesis (score=2.25) and L-isoleucine biosynthesis I pathway (score=2.16) known to benefit immune system. Baseline serum butyrate (aOR:10.00, 95% CI:1.81-107.2) and isoleucine (aOR:1.17, 95% CI:1.04-1.35) significantly associated with extreme-high vaccine response.
Conclusion
Certain gut bacterial species, metabolic pathways and metabolites associate with longer-term COVID-19 vaccine immunogenicity.
MeSH
Sars-Cov-2, Cysteine, Vaccines, Immunogenicity, Vaccine, Isoleucine, Immune System Diseases, Gastrointestinal Microbiome, Microbiota