Key result
Rotarix vaccine will be administered to 1,000 infants in a planned single-arm trial in Vietnam to investigate the impact of human genetic and transcriptional variation on vaccine failure and protective immunity.
Why the study?
Rotavirus vaccines have markedly lower efficacy in low-middle-income countries for unknown reasons, which may be associated with host genetic heritability or gene expression.
This study protocol outlines a large single-arm trial to identify genetic and transcriptomic markers associated with rotavirus vaccine failure in Vietnamese infants.
No immediate clinical implications for rotavirus vaccination; leaves open whether genetic markers predict failure in Vietnamese infants.
Background : Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design : We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion : This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389 . Registered on 16 July 2018.
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Alwis et al. (2020) studied Rotavirus infection (n=1,000). Rotarix vaccine was evaluated on Rotarix vaccine failure events (symptomatic rotavirus infection despite vaccination) from the first dose of vaccination to 18 months. Rotarix vaccine will be administered to 1,000 infants in a planned single-arm trial in Vietnam to investigate the impact of human genetic and transcriptional variation on vaccine failure and protective immunity.
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