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

• Type of Material: Article
• 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
• Language: English
• Date: 2020-07-15
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: Published by Oxford University Press for the Infectious Diseases Society of America 2020.
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jiaa068
• Title of Journal or Parent Work: JOURNAL OF INFECTIOUS DISEASES
• Volume: 222
• Issue: 2
• Start Page: 309
• End Page: 318
• Grant/Funding Information: This work was supported by the Emory University Laney Graduate School (to J. M. B.); and National Institutes of Health National Institute of Allergy and Infectious Diseases (grant number R01AI112970 to B. A. L. and V. E. P.).
• Keywords: SAFETY; Science & Technology; LIVE; DOUBLE-BLIND; immunoglobulin A; Life Sciences & Biomedicine; rotavirus; Infectious Diseases; gastroenteritis; RIX4414; PLACEBO-CONTROLLED TRIAL; VACCINE; correlate of protection; Microbiology; ANTIBODY; vaccination; IMMUNOGENICITY; EFFICACY; 1ST 2 YEARS; Immunology
• Research Categories: Health Sciences, Epidemiology; Biology, Biostatistics

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.