Rotavirus-Specific Immunoglobulin A Responses Are Impaired and Serve as a Suboptimal Correlate of Protection Among Infants in Bangladesh. (31st January 2018)

• Record Type: Journal Article
• Authors: Lee, Benjamin; Carmolli, Marya; Dickson, Dorothy M; Colgate, E Ross; Diehl, Sean A; Uddin, Muhammad Ikhtear; Islam, Shahidul; Hossain, Motaher; Rafique, Tanzeem Ahmed; Bhuiyan, Taufiqur Rahman; Alam, Masud; Nayak, Uma; Mychaleckyj, Josyf C; McNeal, Monica M; Petri, William A; Qadri, Firdausi; Haque, Rashidul; Kirkpatrick, Beth D
• Is Part Of: Clinical infectious diseases. Volume 67:Number 2(2018)
• Page Start: 186
• Page End: 192
• Publication Date: 2018-01-31
• Subjects: rotavirus -- IgA -- vaccination -- correlate of protection -- Prentice criteria; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy076
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : Monovalent oral rotavirus vaccine was poorly immunogenic among infants in Bangladesh. The standard measure of vaccine immunogenicity, rotavirus-specific immunoglobulin A, appeared to be a suboptimal correlate of protection (CoP) in this population, suggesting that improved CoPs are needed.