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
{"title":"Gut microbiota is associated with persistence of longer-term BNT162b2 vaccine immunogenicity.","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","doi":"10.3389/fimmu.2025.1534787","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>BNT162b2 immunogenicity wanes with time and we investigated association between gut microbiota and longer-term immunogenicity.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. <i>Ruminococcus bicirculans</i> (log<sub>10</sub>LDA score=3.65), <i>Parasutterella excrementihominis</i> (score=2.82) and <i>Streptococcus salivarius</i> (score=2.31) were enriched in high-responders, while <i>Bacteroides thetaiotaomicron</i> was enriched in low-responders (score=-3.70). On multivariable analysis, bacterial species (<i>R. bicirculans</i>-aOR: 1.87, 95% CI: 1.02-3.51; <i>P. excrementihominis</i>-aOR: 2.2, 95% CI: 1.18-4.18; S. <i>salivarius</i>-aOR: 2.09, 95% CI: 1.13-3.94) but not clinical factors associated with high response. <i>R. bicirculans</i> 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.</p><p><strong>Conclusion: </strong>Certain gut bacterial species, metabolic pathways and metabolites associate with longer-term COVID-19 vaccine immunogenicity.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1534787"},"PeriodicalIF":5.7000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903479/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2025.1534787","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
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. Ruminococcus bicirculans (log10LDA score=3.65), Parasutterella excrementihominis (score=2.82) and Streptococcus salivarius (score=2.31) were enriched in high-responders, while Bacteroides thetaiotaomicron was enriched in low-responders (score=-3.70). On multivariable analysis, bacterial species (R. bicirculans-aOR: 1.87, 95% CI: 1.02-3.51; P. excrementihominis-aOR: 2.2, 95% CI: 1.18-4.18; S. salivarius-aOR: 2.09, 95% CI: 1.13-3.94) but not clinical factors associated with high response. R. bicirculans 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.
期刊介绍:
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.