Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants.

James A Church, Bernard Chasekwa, Sandra Rukobo, Margaret Govha, Benjamin Lee, Marya P Carmolli, Robert Ntozini, Kuda Mutasa, Monica M McNeal, Florence D Majo, Naume V Tavengwa, Beth D Kirkpatrick, Lawrence H Moulton, Jean H Humphrey, Andrew J Prendergast

Journal: Vaccine 2021;38(13):2870-2878

PMID: 32088018

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Oral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe.

METHODS

Anti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940). SHINE was a cluster-randomized trial of improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) in two rural Zimbabwean districts. Infants received RVV as part of the national immunisation programme. Among HIV-unexposed infants in the non-WASH trial arms, we evaluated associations between potential risk factors (vaccine schedule and dose, maternal and infant nutritional status, infant diarrhoea, and household environment) and RVV immunogenicity (seroconversion, seropositivity and geometric mean titres) using multivariable regression.

RESULTS

Among 219 infants with seroconversion data, 43 (20%) successfully seroconverted and 176 (80%) failed to seroconvert to RVV. Seroconversion was positively associated with a higher length-for-age Z-score (LAZ) around the time of vaccination (adjusted RR 1.27 (95% CI 1.04, 1.55), P = 0.021), and negatively associated with concurrent OPV and RVV administration (adjusted RR 0.36 (0.19, 0.71), P = 0.003). Among 472 infants with post-vaccination titres, a higher LAZ score was associated with increased seropositivity (aRR 1.21 (95% CI 1.06, 1.38), P = 0.004), and higher birthweight was associated with increased IgA titres (0.45 (95%CI 0.18, 1.09) U/mL greater per 100 g gain in birthweight; P = 0.001).

CONCLUSIONS

Infant ponderal and linear growth were positively associated with RVV immunogenicity, while concurrent administration of OPV was negatively associated with RVV immunogenicity. Together, these findings suggest that improving foetal growth and separating RVV and OPV administration are plausible approaches to increasing RVV immunogenicity.

Address: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Centre for Genomics & Child Health, Blizard Institute, Queen Mary University of London, UK. Electronic address: [email protected].; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.; Vaccine Testing Center, Department of Pediatrics, Larner College of Medicine, University of Vermont, Burlington, VT, USA.; Vaccine Testing Center, Department of Microbiology & Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT, USA.; Department of Pediatrics, University of Cincinnati College of Medicine, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Centre for Genomics & Child Health, Blizard Institute, Queen Mary University of London, UK; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: [email protected].

DOI: 10.1016/j.vaccine.2020.01.097

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MeSH Terms: Antibodies, Viral, Child, Preschool, Female, Humans, Immunogenicity, Vaccine, Immunoglobulin A, Infant, Male, Pregnancy, Rotavirus, Rotavirus Infections, Rotavirus Vaccines, Zimbabwe