Publication Date
1-1-2024
Journal
Cellular and Molecular Gastroenterology and Hepatology
DOI
10.1016/j.jcmgh.2024.101393
PMID
39179176
PMCID
PMC11462264
PubMedCentral® Posted Date
8-22-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Rotavirus Vaccines, Gastrointestinal Microbiome, Humans, Mice, Rotavirus Infections, Vaccine Efficacy, Rotavirus, Fecal Microbiota Transplantation, Female, Antibodies, Viral, Vaccination, Male, Feces, Child, Preschool, Disease Models, Animal, Microbiota, Segmented Filamentous Bacteria, Seroconversion
Abstract
BACKGROUND & AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.
METHODS: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMTs) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge.
RESULTS: SFB colonization induced a phenotype that was reminiscent of RV vaccine failure (ie, failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished). FMTs from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMTs from high-responsive vaccinees copiously shed RV antigens and robustly generated anti-RV antibodies following RV vaccination. Concomitantly, such mice were impervious to RV challenge. In contrast, mice receiving FMTs from children who had not responded to RV vaccination exhibited only modest responses to RV vaccination and, concomitantly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested involvement of Clostridium perfringens. Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of published microbiome data found C. perfringens abundance in children modestly associated with RV vaccine failure.
CONCLUSION: Microbiota composition influences RV vaccine efficacy with C. perfringens being one, perhaps of many, potential contributing taxa.
Graphical Abstract