Despite significant progress in prevention and treatment, malaria remains a major global health threat, causing an estimated 610,000 deaths globally in 2024, with young children in sub‑Saharan Africa disproportionately affected.
Malaria is a shape‑shifting enemy, the parasite Plasmodium falciparum moves through several distinct stages, beginning as sporozoites transmitted by the bite of an infected mosquito, then infecting and multiplying in the liver, before emerging into the bloodstream to invade and replicate within red blood cells. A single‑stage vaccine, like the currently recommended RTS,S/AS01 or R21/Matrix-M vaccines, targets only one stage in that complex lifecycle.
Now, the University of Oxford, the Clinical Research Unit of Nanoro and EVI have launched two new clinical trials to test a next‑generation multi-stage malaria vaccine designed to target two stages together two in the Plasmodium falciparum lifecycle. The trials include a Phase 1b study (VAC093) that will evaluate different combinations of R21 – the Malaria vaccine produced by the Serum Institute of India (SIIPL) and based on the R21 antigen developed by the University of Oxford - and the blood-stage vaccine candidates RH5.1and R78C developed by the Draper Lab, also at the University of Oxford. In addition, there is a Phase 2b study (VAC087) to generate the first efficacy data on R78C alone and in combination with the RH5.1 and R21 vaccines (all vaccines administered with Matrix-M® adjuvant).
The VAC093 trial aims to assess the safety and immunogenicity of the blood-stage malaria vaccine candidates R78C and RH5.1 combined with R21/Matrix-M in adults aged 18-35 years and children aged 5-17 months in Burkina Faso (Phase 1b age de-escalation, open-label study). The trial started in September 2025. After safety data review of the Phase 1 b trial (VAC093, NCT06958198), the independent data safety monitoring board (DSMB) gave their green light for the Phase 2phase b trial (VAC087, NCT07183371) vaccinations to start in December 2025. VAC087 is a randomised controlled trial to assess the safety, immunogenicity and efficacy of the malaria vaccine candidate R78C alone with Matrix-M, and the combination of R78C plus RH5.1 with Matrix-M given alongside R21 with Matrix-M, in children aged 5-36 months in Burkina Faso.
The two clinical trials are sponsored by the University of Oxford with Prof. Angela Minassian as the Chief Investigator and are being conducted at the Institut de Recherche en Sciences de la Santé – Clinical Research Unit of Nanoro (IRSS-URCN), in Burkina Faso, led by Principal Investigator Prof. Halidou Tinto and study coordinator Associate Prof. Magloire Natama.
Professor Angela Minassian, Chief Investigator of the trials, said: “Malaria continues to claim hundreds of thousands of lives each year, and while the current licensed vaccines are making a significant impact, they do not provide 100% protection. These trials will provide the first critical evidence on whether a multi-stage approach can safely enhance and extend protection in young children, who are at greatest risk. Working in close partnership with our colleagues in Nanoro and with the support of EVI, we hope to generate the data needed to inform the next generation of malaria vaccines and move closer to the long-term goal of malaria elimination.”
Prof. Halidou Tinto, Director of Research in parasitology and Regional Director of the Institut de Recherche en Sciences de la Santé (IRSS), Nanoro, based in Burkina Faso, said: “Despite substantial progress since 2000, malaria remains a major public health problem in sub-Saharan Africa. It affects disproportionately the more vulnerable people, including pregnant women and young children. Protecting the latter will help them to grow up healthier. After the results reported last year on the RH5.1/Matrix-M that has shown encouraging efficacy and safety profiles, the newly initiated VAC093 and VAC087 trials will accelerate the development of the first multistage malaria vaccines. As the trial site of these new trials, we are proud to be the leading institution in sub-Saharan Africa, together with our European partners, to achieve this important milestone, which will open the perspectives to reach in the future the dream of an African continent free of malaria.”
The trials were initiated as part of the EDCTP2-funded multi-stage malaria vaccine consortium (MMVC) with further support from the Wellcome Trust. Following the end of MMVC in December 2025, the trials will now continue with financial support from EVI, with funding obtained from Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR) through KfW. Besides co-funding both trials, EVI is taking on a larger role covering monitoring (with support of the CRO Pharmalys Ltd), DSMB support, communication and quality management planning, risk assessment, and meeting organisation in the Phase 2b trial.
Dr Irene Nkumama, Malaria programme manager at EVI, said: “The European Vaccine Initiative is proud to collaborate with our partners in Oxford and Nanoro on two multi-stage malaria vaccine clinical trials aimed at advancing the next generation of tools to combat this devastating disease. As a Product Development Partnership, these joint efforts reflect our commitment to mobilise funding for global health priorities such as malaria vaccine development and to collaborate with leading global partners to accelerate the development of safe, effective, and affordable vaccines for the communities that need them most.”
The two clinical trials will generate critical evidence on how best to combine the R21/Matrix-M vaccine, developed by SIIPL, with one or two blood‑stage components, helping identify the most promising multi‑stage vaccine approach. The studies will also deliver early proof of concept that a multi‑stage malaria vaccine is safe and can improve protection. If the initial results are positive, this candidate could move rapidly into larger trials, accelerating the development of a new tool with strong potential to reduce malaria illness and deaths.
Acknowledgment:
VAC093: NCT06958198 and VAC087: NCT07183371 studies receive support from European and Developing Countries Clinical Trials Partnership (EDCTP, RIA2016V-1649 MMVC) ), the Wellcome Trust and BMFTR (Bundesministerium für Forschung, Technologie und Raumfahrt) via KFW. Draper Lab also receives funding support for clinical vaccine development from Coefficient Giving.