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  • Review Article
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Malaria vaccines: a new era of prevention and control

Nature Reviews Microbiology volume 22, pages 756–772 (2024)Cite this article

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Abstract

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.

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Fig. 1: Malaria vaccine classes targeting different stages of the parasite life cycle with associated bioassays.
Fig. 2: Circumsporozoite protein is the major surface antigen of sporozoites and the target for several vaccines and therapeutic human monoclonal antibodies.
Fig. 3: Whole-sporozoite malaria vaccines targeting sporozoites and liver-stage parasites.
Fig. 4: Blood-stage and mosquito-stage vaccines.
Fig. 5: The vaccine development funnel.

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Acknowledgements

The authors thank their colleagues from the Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases (LMIV–NIAID) for the discussions, ideas and vaccine development contributions that informed the content of this manuscript. A. Hoofring from NIH Medical Arts prepared the main figures. R. Morrison (LMIV–NIAID) prepared Supplementary Fig. 1. The authors are supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

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  1. Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Patrick E. Duffy, J. Patrick Gorres, Sara A. Healy & Michal Fried

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All authors researched data for the article and contributed substantially to discussion of the content. P.E.D. wrote the first draft with contributions from all authors. All authors reviewed and/or edited the manuscript before submission.

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Duffy, P.E., Gorres, J.P., Healy, S.A. et al. Malaria vaccines: a new era of prevention and control. Nat Rev Microbiol 22, 756–772 (2024). https://doi.org/10.1038/s41579-024-01065-7

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