Postvaccination Serum Antirotavirus Immunoglobulin A as a Correlate of Protection Against Rotavirus Gastroenteritis Across Settings

• Authors: Julia M Baker, Emory University; Jacqueline E Tate, Centers for Disease Control and Prevention, Atlanta; Juan Leon, Emory University; Michael Haber, Emory University; Virginia E Pitzer, Yale University; Benjamin Lopman, Emory University
• Journal Title: JOURNAL OF INFECTIOUS DISEASES
• Volume: Volume 222, Number 2
• Publisher: OXFORD UNIV PRESS INC | 2020-07-15, Pages 309-318
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1093/infdis/jiaa068
• Subjects: Health Sciences, Epidemiology; Biology, Biostatistics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Microbiology; rotavirus; vaccination; correlate of protection; gastroenteritis; immunoglobulin A; 1ST 2 YEARS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; VACCINE; EFFICACY; SAFETY; LIVE; IMMUNOGENICITY; ANTIBODY; RIX4414

Abstract

Background: 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 postvaccine serum antirotavirus immunoglobulin A (IgA) as an individual-level immune correlate of protection against rotavirus gastroenteritis. Methods: Individual-level data on 5074 infants in 9 GlaxoSmithKline Rotarix Phase 2/3 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. Results: Seroconversion (IgA≥20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis to age 1 year. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR,0.04; 95% confidence interval [CI],. 01-.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (HR, 0.46; 95% CI,. 25-.86). As IgA threshold increased, risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings. Discussion: Postvaccination antirotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis to age 1 year. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance.