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

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

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.

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

Figure 2.

Factors significantly associated with rotavirus-specific…

Figure 2.

Factors significantly associated with rotavirus-specific immunoglobulin A seropositivity. Values shown represent adjusted odds…

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.
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.

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Source: PubMed

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