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Development of an effective malaria vaccine

In spite of all the efforts over many years and decades to reduce malaria infection and deaths, the latest data from the World Health Organization (WHO) still show that in 2020 there were 241 million cases and 627 000 deaths. Of which, 95% of cases and 96% of deaths were in sub-Saharan Africa; 80% of deaths occur in children under the age of 5 years old.

As we know, malaria is caused by the unicellular protozoan parasites of the Plasmodium genus, with most deaths caused by P. falciparum, with transmission to humans resulting from bites from infected female Anopheles mosquitos. The development of an effective vaccine against malaria has been hampered by the complexity of both the Plasmodium genome and the parasite’s life cycle. Early work to produce a vaccine based on parasites attenuated by irradiation ultimately proved to be successful but is logistically impractical for large-scale delivery. Subsequent other attempts at vaccines have produced glimmers of hope but have struggled to produce an antibody response. More recently, the circumsprozoite protein (CSP) has been the antigen of choice as its structure and function are highly conserved and it is involved in the early preerythrocyte phase of infection. One such vaccine, RTS,S/AS01 (Mosquirix; developed by PATH Malaria Vaccine Initiative and GlaxoSmithKline with support from the Bill and Melinda Gates Foundation) consists of parts of the CSP repeat (R), T-cell epitopes (T) and hepatitis B viral surface antigen (S) along with a chemical adjuvant AS01. In trials, this vaccine had an efficacy of 68% over a period of 6 months following administration of the initial three doses, and (although vaccine efficacy wanes considerably) it was approved for use in children by the WHO in 2015. However, this month, results from a phase 1/2b randomized controlled trial of the R21/Matrix-M vaccine (developed by the University of Oxford in collaboration with others) have been published1. The R21 vaccine also uses the CSP antigen but at a higher proportion than the RTS,S vaccine, and it includes the Matrix-M adjuvant that is also used in the Novavax COVID-19 vaccine. The results show that an initial three doses followed by a booster a year later gives up to 80% protection, meaning that we finally have a vaccine against malaria that meets the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children, which is very welcome news.

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Datoo MS, Natama HM, Somé A et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. Lancet Infect Dis 2022:S1473-3099(22)00442-X (