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Randomized Controlled Trial
. 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

Benjamin Lee  1 , Marya Carmolli  2 , Dorothy M Dickson  2 , E Ross Colgate  2 , Sean A Diehl  2 , Muhammad Ikhtear Uddin  3 , Shahidul Islam  3 , Motaher Hossain  3 , Tanzeem Ahmed Rafique  3 , Taufiqur Rahman Bhuiyan  3 , Masud Alam  3 , Uma Nayak  4 , Josyf C Mychaleckyj  4 , Monica M McNeal  5 , William A Petri  6 , Firdausi Qadri  3 , Rashidul Haque  3 , Beth D Kirkpatrick  2
Affiliations
Randomized Controlled Trial

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

Benjamin Lee et al. Clin Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Rotavirus-specific immunoglobulin A (RV-IgA) geometric mean concentration (U/mL) among all, seropositive, and seroconverted children at week 18 of life. Dashed line represents 20 U/mL, the threshold for seropositivity. Seroconversion was defined as week 18 RV-IgA ≥20 U/mL with week 6 RV-IgA <20 U/mL. Abbreviations: CI, confidence interval; GMC, geometric mean concentration.
Figure 2.
Figure 2.
Factors significantly associated with rotavirus-specific immunoglobulin A seropositivity. Values shown represent adjusted odds ratios (x-axis) with corresponding 95% confidence intervals in a multivariable model that included 10 variables significant in univariate analysis at P < .125. Abbreviations: EBF, exclusive breastfeeding; RV-IgG, rotavirus-specific serum immunoglobulin G.
See this image and copyright information in PMC

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