Seasonal mass vaccination with R21/Matrix-M for malaria elimination (SERVAL): protocol of the cluster randomised trial

Introduction Progress in malaria control has stalled since 2015, highlighting the need for new control tools. The R21/Matrix-M (R21) malaria vaccine, a pre-erythrocytic vaccine recently approved by WHO for small children, may be one of these tools. This trial aims to assess whether seasonal mass vaccination with R21 reduces malaria transmission in The Gambia and Burkina Faso, two countries at the extreme of the transmission spectrum. Methods This is a multi-centre open cluster-randomised controlled trial to assess the impact of mass vaccination with R21 on malaria transmission and morbidity. The trial will be implemented in eastern Gambia (low to moderate transmission), and Central Burkina Faso (intense transmission). Thirty medium-sized villages in The Gambia and 24 in Burkina Faso will be randomised (1:1) to either intervention or control arm. All eligible residents in intervention villages will receive R21 vaccinations in three-monthly rounds, from May to July 2024, prior to the malaria transmission season. A booster vaccine dose will be administered the following year, in June 2025. The primary outcome is malaria prevalence at peak transmission (November 2024). Secondary outcomes include safety and tolerability, incidence of clinical malaria, vaccination coverage and community acceptability, cost and cost-effectiveness of the intervention. Discussion This is the first trial on seasonal mass vaccination aiming at reducing malaria transmission. Strengths of the study include its design as an adequately powered cluster-randomized trial and the inclusion of study sites with differing transmission intensity which will also provide safety and efficacy data for different age groups. Key challenges remain vaccine hesitancy and vaccination coverage. If successful, R21 seasonal mass vaccination will be an innovative intervention to accelerate malaria elimination efforts and reach the goal set in the Global Technical Strategy for malaria 2016-2030. Trial registration Clinical trials.gov, NCT06578572. Registered on 27 March 2024