Malaria vaccines: a new era of prevention and control

Malaria killed over 600,000 people in 2022, a death toll that has not improved since 2015. Additionally, parasites and mosquitoes resistant to existing interventions are spreading across Africa and other regions. Vaccines offer hope to reduce the mortality burden: the first licensed malaria vaccines, RTS,S and R21, will be widely deployed in 2024 and should substantially reduce childhood deaths. In this Review, we provide an overview of the malaria problem and the Plasmodium parasite, then describe the RTS,S and R21 vaccines (the first vaccines for any human parasitic disease), summarizing their benefits and limitations. We explore next-generation vaccines designed using new knowledge of malaria pathogenesis and protective immunity, which incorporate antigens and platforms to elicit effective immune responses against different parasite stages in human or mosquito hosts. We describe a decision-making process that prioritizes malaria vaccine candidates for development in a resource-constrained environment. Future vaccines might improve upon the protective efficacy of RTS,S or R21 for children, or address the wider malaria scourge by preventing pregnancy malaria, reducing the burden of Plasmodium vivax or accelerating malaria elimination. In this Review, Duffy et al. examine the malaria vaccine landscape, showcasing both achievements and setbacks over the past decades. They discuss approaches and assays for different parasite stages, summarize recent advancements, propose a decision-making process for the field and identify future priorities to address unmet needs.