A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of post-vaccine serum anti-rotavirus immunoglobulin A (IgA) that serves as an individual-level immune correlate of protection against rotavirus gastroenteritis.
Individual-level data on 5,074 infants enrolled in nine GlaxoSmithKline Rotarix Phase II/III clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis.
Seroconversion (IgA ≥20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis up to 1 year of age. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR=0.04, 95% confidence interval (CI)=0.01-0.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (0.46, 0.25-0.86). As the IgA threshold increased, the risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings.
Post-vaccination anti-rotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis up to 1 year of age. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance.

Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.