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Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi

Pollock, Louisa; Bennett, Aisleen; Jere, Khuzwayo C; Mandolo, Jonathan; Dube, Queen; Bar-Zeev, Naor; Heyderman, Robert S; ... Iturriza-Gomara, Miren; + view all (2022) Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi. Clinical Infectious Diseases 10.1093/cid/ciab895. (In press).

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Abstract

BACKGROUND: Rotavirus vaccine efficacy is reduced in low-income populations, but efforts to improve vaccine performance are limited by lack of clear correlates of protection. While plasma rotavirus (RV)-specific IgA appears strongly associated with protection against rotavirus gastroenteritis in high-income countries, weaker association has been observed in low-income countries. We tested the hypothesis that lower RV-specific IgA is associated with rotavirus vaccine failure in Malawian infants. METHODS: In a case-control study we recruited infants presenting with severe rotavirus gastroenteritis following monovalent oral rotavirus vaccination (RV1 vaccine failures). Conditional logistic regression was used to determine the odds of rotavirus seronegativity (RV-specific IgA<20 U/mL) in these cases compared 1:1 with age-matched, vaccinated, asymptomatic community controls. Plasma RV-specific IgA was determined by ELISA for all participants at recruitment, and for cases at 10 days post symptom onset. Rotavirus infection and genotype were determined by antigen testing and RT-PCR respectively. RESULTS: In 116 age-matched pairs, infants with RV1 vaccine failure were more likely to be RV-specific IgA seronegative than controls: OR 3.1 (95%CI 1.6-5.9), p=0.001. In 60 infants with convalescent serology, 42/45 (93%, 95%CI 81-98%) infants seronegative at baseline became seropositive. Median rise in RV-specific IgA concentration following acute infection was 112.8 (IQR 19.1-380.6) fold. CONCLUSIONS: In this vaccinated population with high residual burden of rotavirus disease, RV1 vaccine failure was associated with lower RV-specific IgA, providing further evidence of RV-specific IgA as a marker of protection. Robust convalescent RV-specific IgA response in vaccine failures suggests differences in wild-type and vaccine-induced immunity, which informs future vaccine development.

Type: Article
Title: Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi
Location: United States
DOI: 10.1093/cid/ciab895
Publisher version: http://doi.org/10.1093/cid/ciab895
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Microbiology, rotavirus, IgA, vaccine, Malawi, gastroenteritis, ANTIROTAVIRUS IMMUNOGLOBULIN-A, DOUBLE-BLIND, GASTROENTERITIS, IMMUNOGENICITY, SERUM, LIVE, PROTECTION, INFECTION, CHILDREN, SAFETY
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10153222
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