Early-life gut microbiome composition and rotavirus vaccine-induced IgA responses in U.S. infants: a longitudinal cohort study.

BACKGROUND

Rotavirus remains a leading cause of childhood mortality worldwide, despite the widespread introduction of oral rotavirus vaccines. Evidence linking the gut microbiome to vaccine response is inconsistent and limited in U.S.

POPULATIONS: This study investigates the development of the infant gut microbiome and its association with immunogenicity following RotaTeq administration in U.S. infants.

METHODS

We conducted a longitudinal analysis of infants in Rochester, New York, using 16S rRNA sequencing to assess microbiome composition at one (M1), sixth (M6), and twelfth (M12) months of age. Rotavirus-IgA serologies were measured at M6 and M12 to assess RotaTeq vaccine seroresponse. Clinical metadata were used to assess factors associated with microbial diversity and rotavirus-IgA titres over the first year of life. We examined associations between (1) M1 microbiome and M6 rotavirus-IgA; (2) M6 microbiome and M6 rotavirus-IgA; and (3) M6 microbiome and M12 rotavirus-IgA.

FINDINGS: Higher gut microbial alpha diversity at M1 was associated with higher rotavirus-IgA titres at M6 (N = 47, β: 2·06, 95% CI: [0·31-3·99], p = 0·024). Alpha diversity at M6 was not associated with concurrent rotavirus-IgA responses (N = 56, β: 0·73, 95% CI: [-0·856, 2·313], p = 0·36) but was associated with higher rotavirus-IgA at M12 (N = 52, β: 1·47, 95% CI: [0·127, 2·805], p = 0·033). Rotavirus-IgA responses were associated with specific microbial taxa across timepoints, with both positive and negative associations observed.

INTERPRETATION: In a healthy U.S. infant cohort, early-life gut microbiome diversity and composition were associated with rotavirus-IgA responses following RotaTeq vaccination. This study advances understanding of microbiome-vaccine interactions in high-income settings.

FUNDING: Office of the Director of the National Institutes of Health, National Institute of Mental Health of the National Institutes of Health, and the National Center for Advancing Translational Sciences of the National Institutes of Health.