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.