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Clin Infect Dis. 2018 Jul 2;67(2):186-192. doi: 10.1093/cid/ciy076.

Rotavirus-Specific Immunoglobulin A Responses Are Impaired and Serve as a Suboptimal Correlate of Protection Among Infants in Bangladesh.

Author information

1
Department of Pediatrics, Vaccine Testing Center, University of Vermont Larner College of Medicine, Burlington.
2
Department of Medicine, Vaccine Testing Center, University of Vermont Larner College of Medicine, Burlington.
3
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
4
Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia, Charlottesville.
5
Laboratory of Specialized Clinical Studies, Cincinnati Children's Hospital Medical Center, Ohio.
6
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville.

Abstract

Background:

Rotavirus (RV)-specific immunoglobulin A (IgA) responses following oral RV vaccination are impaired in low-income countries, where the utility of RV-IgA as a correlate of protection (CoP) remains unclear. In a monovalent oral RV vaccine (Rotarix) efficacy trial among infants in Dhaka, Bangladesh, we identified factors associated with poor RV-IgA responses and explored the utility of RV-IgA as a CoP.

Methods:

Infants were randomized to receive Rotarix or no Rotarix at 10 and 17 weeks of life and followed with active diarrheal surveillance. RV-IgA concentration, seroconversion, and seropositivity were determined at 18 weeks of life and analyzed for correlation(s) with rotavirus diarrhea (RVD) and for contribution to Rotarix vaccine effect.

Results:

Among vaccinated infants, overall RV-IgA geometric mean concentration was 21 U/mL; only 27% seroconverted and 32% were seropositive after vaccination. Increased RV-specific maternal antibodies significantly impaired immunogenicity. Seroconversion was associated with reduced risk of RVD through 1 year of life, but RV-IgA seropositivity only explained 7.8% of the vaccine effect demonstrated by the clinical endpoint (RVD).

Conclusions:

RV-IgA responses were low among infants in Bangladesh and were significantly impaired by maternal antibodies. RV-IgA is a suboptimal CoP in this setting; an improved CoP for RV in low-income countries is needed.

Clinical Trials Registration:

NCT01375647.

PMID:
29394355
PMCID:
PMC6030840
DOI:
10.1093/cid/ciy076
[Indexed for MEDLINE]
Free PMC Article

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