Project: A randomized controlled trial of two versus three doses of Rotarix™ vaccine for boosting and longevity of vaccine immune responses in Zambia

Acronym ROVAS-2 (Reference Number: TMA2016SF-1511)
Duration 01/04/2018 - 31/03/2022
Project Topic Diarrhoea is the second largest killer of children in the world and rotavirus is the most common cause of severe dehydrating diarrhoea among children <5 years of age globally. Rotavirus vaccines, such as Rotarix? and RotaTeq?, are currently available tools that many countries have introduced into their national immunization schedules and which have shown significant impact on reduction of rotavirus associated diarrhoea morbidity and hospitalisations. However, despite the successes, these vaccines are proving to have lower immunogenicity, efficacy, effectiveness and duration of protection in low middle income country (LMIC) children as compared to those in high income countries. Improvements in the performance of these vaccines already in routine public use in LMICs would have even greater public health benefits in these settings. We propose a randomised controlled trial to test the hypothesis that a third dose of Rotarix™ administered at 9 months’ infant age will boost rotavirus specific Immunoglobulin A (RV-IgA) by 1-year of infant age and potentially enable provision of longer lasting immunity. A total of 212 Zambian mother-infant pairs at 6 weeks infant age will be recruited just before their first Rotarix™ vaccine dose following a clear inclusion/exclusion criteria and written informed consent. Baseline characteristics, physical anthropometric examination, blood and saliva samples to characterize the infant innate and adaptive immune response and genetic predispositions to rotavirus infection will be obtained during the follow up period until the infant is 2 years old. At 9 months of age, half of the infants will be randomly allocated to receive a third dose of Rotarix™. The primary outcome will be assessed at 12 months infant age and analysis will be based on intent-to-treat population. Simple linear regression of log-transformed RV IgA titre at 12-month infant age will be used to estimate geometric mean ratio and 95% confidence interval (CI) and perform a two-sample t-test between the two arms. Adjusted geometric mean ratio will also be presented for baseline characteristics that appear to have imbalance between the two arms. The specific aims are as follows: 1. To compare serum RV-IgA at 12 months infant age between two doses of oral Rotarix™ administered at 6 & 10 weeks of infant age (standard of care arm) and three doses administered at 6 weeks, 10 weeks, & 9 months of infant age (experimental arm). 2. To assess the incidence of solicited and unsolicited adverse events following third dose of Rotarix™ 3. To profile rotavirus specific B and T lymphocyte phenotypes, Secretory IgA response and cytokine signatures to characterize the immune responses to rotavirus vaccine among seroconverting and nonseroconverting immunised Zambian infants. 4. To evaluate the effect of diarrhoeal disease on the growth velocity of infants 5. To contribute to research capacity strengthening through specific training of one PhD and one MSc student through this project. Clinical outputs of this trial will address potential recommendations on dose regimen for Rotarix™ vaccines in LMIC for boosting of immune responses and longer lasting clinical protection against rotavirus disease. By profiling immune response post vaccination over time the study would also provide a means of identification of potential correlates of vaccine protection. The project will build capacity through training of 1 PhD and 1 MSc CIDRZ staff at the University of Zambia.This EDCTP Senior Fellowship will facilitate an African researcher to conduct the proposed clinical trial addressing important scientific questions that are cutting edge to the field of rotavirus vaccines and applicable to Zambia as well as other LMIC settings. The success of the proposed trial will contribute in establishing the Fellow as an authentic research leader in Zambia, and within the African sub-region on rotavirus research.
Network EDCTP2
Call Senior Fellowships 2016

Project partner

Number Name Role Country
1 Centre for Infectious Disease Research in Zambia Limited Coordinator Zambia
1 Centre for Infectious Disease Research in Zambia Limited Coordinator Zambia