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. Although plasma rotavirus (RV)-specific immunoglobulin A ( 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 enzyme-linked immunosorbent assay for all participants at recruitment, and for cases at 10 days after symptom onset. Rotavirus infection and genotype were determined by antigen testing and reverse transcription-polymerase chain reaction, respectively. RESULTS: In 116 age-matched pairs, infants with RV1 vaccine failure were more likely to be RV-specific IgA seronegative than controls: odds ratio, 3.1 (95% confidence interval [CI], 1.6-5.9), P=.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 (interquartile range, 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.
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Authors | Louisa Pollock, Aisleen Bennett, Khuzwayo C Jere, Jonathan Mandolo, Queen Dube, Naor Bar-Zeev, Robert S Heyderman, Nigel A Cunliffe, Miren Iturriza-Gomara |
Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
(Clin Infect Dis)
Vol. 75
Issue 1
Pg. 41-46
(08 24 2022)
ISSN: 1537-6591 [Electronic] United States |
PMID | 34788820
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected]. |
Chemical References |
- Immunoglobulin A
- Rotavirus Vaccines
- Vaccines, Attenuated
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Topics |
- Case-Control Studies
- Gastroenteritis
(epidemiology, prevention & control)
- Humans
- Immunoglobulin A
- Infant
- Malawi
(epidemiology)
- Rotavirus
(genetics)
- Rotavirus Infections
(epidemiology, prevention & control)
- Rotavirus Vaccines
- Vaccines, Attenuated
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