Rotavirus-specific IgA and IgG Patterns During the First Two Years of Life in the PREVAIL Birth Cohort.

Abstract

Mitigating the underlying causes of differential immunity from rotavirus infection and vaccination requires a comprehensive understanding of rotavirus natural history and immune response. A US-based birth cohort provides a unique opportunity to longitudinally examine rotavirus immune response. Serum was collected from children at birth (cord blood), 6 weeks, and 6, 12, 18 and 24 months of age. Maternally-derived rotavirus-specific IgG (birth samples) and rotavirus-specific IgA and IgG (6-week through 24-month samples) were measured via enzyme immunoassay. Stool samples were collected weekly and during episodes of acute gastroenteritis to identify rotavirus infections. Serum samples prior to and after infection or vaccination were compared to assess their impact on IgA geometric mean titers (GMT). A Generalized Estimating Equation was fit to identify predictors of IgA GMT. The median change in IgA GMT from vaccination comparing 6-week and 6-month samples was 38.4 U/mL [IQR 4.4-138.1]. The change in IgA following infection varied widely (median=64.5 [IQR-2.0-192.9]) with pre- and post-infection GMTs of 35.7 U/mL (95% CI:21.4-59.6) and 102.6 U/mL (95% CI:41.1-256.0), respectively. In adjusted analyses, IgA GMT was higher when mother and/or child was a secretor (ratio of means (RoM)=1.3, 95% CI: 1.1-1.4) compared to non-secretor mother-child pairs. Being fully vaccinated was more strongly associated with IgA GMT in the first (RoM=1.9, 95% CI: 1.7-2.0) compared to the second year of life (RoM=1.3, 95% CI: 1.0-1.7). This longitudinal assessment of rotavirus-specific immune response contributes to our understanding of multifactorial drivers of rotavirus immunity in a post-vaccine setting.