Phase 1 clinical trials in the UK and Burkina Faso showed that the malaria vaccine candidate, R21 adjuvanted with Matrix-M, has an acceptable safety profile with strong immunogenicity and was well tolerated in adults. These data paved the road for efficacy testing of this vaccine leading to vaccine licensure.

EVI，31 January 2025

Malaria remains a substantial public health burden. Globally in 2023, there were an estimated 263 million malaria cases and 597 000 malaria deaths in 83 countries. The WHO African Region is carrying a disproportionately high share of the global malaria burden with 94% of malaria cases (246 million) and 95% (569 000) of malaria deaths with about 76% of the malaria deaths in children under 5 years of age in 2023, according to the World malaria report 2024.

At the time of the study, RTS,S/AS01B (RTS,S) was the first malaria vaccine to show protection  against clinical disease episodes in young children in a phase 3 clinical trial. However, the vaccine had not yet been approved.

Meanwhile, the development of R21 in Matrix-M adjuvant malaria vaccine was launched as an alternative approach to RTS,S.

R21 is an anti-sporozoite malaria vaccine composed of nanoparticles, formed from a circumsporozoite protein and hepatitis B surface antigen (HBsAg) fusion protein. It is administered with the saponin based Matrix-M adjuvant. This adjuvant has now been previously tested with other (non-malaria) vaccine candidates and has demonstrated safety in millions of individuals who received COVID-19 vaccines.  

Here, we report the first two phase 1 clinical trials of R21, one conducted in malaria-naive individuals in the United Kingdom (UK) and the other in semi-immune adults from an area of very high malaria transmission in Burkina Faso with the aim to assess the safety and immunogenicity of R21 in Matrix-M adjuvant. Both trials are registered with ClinicalTrials.gov, NCT02572388 for phase 1a and NCT02925403 for phase 1b, and are completed.

A favourable vaccine safety profile was identified in both UK and Burkinabe adults with minimal reactogenicity and a much reduced incidence of post-vaccination fever compared with RTS,S. Antibody responses to malaria induced by R21/Matrix-M were not different to those induced by RTS,S even when using five-fold and 25-fold less immunogen.

Since this study was undertaken, clinical development of R21/Matrix-M has continued with a phase 2b efficacy trial in Burkina Faso in children aged 5–17 months  and a multisite phase 3 trial demonstrating that R21/Matrix-M is an alternative malaria vaccine to RTS,S with similar or better efficacy.

Based on these data, several African countries have now licensed R21/Matrix-M. As of early December 2024, the WHO reports that 17 countries have introduced both RTS,S and R21/Matrix-M malaria vaccines into routine childhood immunisation programs, with additional nations planning to follow this year with support from Gavi, the Vaccine Alliance, and WHO. The full impact of these vaccines on malaria mortality and morbidity will only be realised in coming years as their introduction and coverage expand in areas with high to moderate malaria transmission.

We invite you to read the full article here: https://doi.org/10.1016/s2666-5247(24)00084-3

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 The research leading to these results has received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under grant agreement n°[305282]

and from the European and Developing Countries Partnership (Field Trials of a New Combination Malaria Vaccine in West African Adults and Children (MVVC2); grant number SP.2011.41304.025) with co-funding from Swedish International Development Cooperation Agency; UK Medical Research Council; Irish Aid, Department of Foreign Affairs and Trade, Ireland, and Bundesministerium für Bildung und Forschung, Germany (01KA1501; 01KA1301).

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This article is reprinted with permission from the European Vaccine Initiative (EVI), for educational and communication purposes only. Original link: https://www.euvaccine.eu/post/publication-of-first-in-human-data-of-malaria-vaccine-candidate-r21-in-matrix-m-adjuvant. Copyright belongs to the original author.