A new landscape for malaria vaccine development

the World Health Organization (WHO) recommended the first vaccine against malaria to prevent Plasmodium falciparum malaria in children living in areas with moderate to high transmission 1, a watershed moment in child health. This historic event was informed by results of WHO pilot implementation of the RTS, S vaccination in Ghana, Kenya, and Malawi, that documented feasibility to deliver through routine immunization systems, capacity to increase equity to malaria prevention, a strong safety profile, significant reduction in severe malaria, and high cost effectiveness 2. More recent analysis of the RTS, S pilot implementation results demonstrated 13% all-cause mortality reduction even in the presence of only moderate vaccine coverage 3. Enthusiasm for RTS, S implementation in endemic countries has resulted in 18 country approvals to date for Gavi support for vaccine introduction, and current limited supply through 2025 was allocated to 12 of these countries 4. Two years later, the WHO recommended a second malaria vaccine R21/Matrix-M (R21) on October 2, 2023 5. Like RTS, S, R21 generates immunity to P. falciparum circumsporozoite protein (CSP). A recent Phase 3 clinical trial of R21 in children 5 to 36 months of age demonstrated 75% efficacy at 2 sites with seasonal transmission and 68% efficacy at 3 sites with perennial transmission 6. While RTS, S and R21 have not been compared head-to-head, they are expected to perform similarly and substantially impact malaria morbidity and mortality in endemic areas. R21 has a significant cost advantage at US 2 to 4 per dose and is expected to fill the huge demand-supply gap. Now, with 2 high-impact malaria vaccines becoming available, how has this milestone influenced malaria vaccine research and development efforts? This article aims to explain more about the current landscape of malaria vaccine development.