A new R21/Matrix-M malaria vaccine shows 75% efficacy in a Phase2b trial – a potentially game-changing result compared to the WHO-approved RTS,S/AS01 (RTS,S) vaccine.
The WHO has said it will continue with the rollout of its approved RTS,S vaccine, despite the promise of a new malaria vaccine candidate, the R21/Matrix-M, that shows an efficacy of 75% in a recent Phase 2b trial – nearly double that of the recently-approved RTS,S vaccine.
At a WHO press briefing, Dr Matshidiso Moeti, WHO’s regional director for Africa, welcomed the findings on the R21/Matrix-M vaccine, which were published in the Lancet, but said the rollout of the RTS,S vaccine would continue.
The R21/Matrix M vaccine candidate still must be tested clinically against the RTS,S vaccine in a large-scale field setting, Moeti said.
“We can look forward to – eventually once the data is finalized – the vaccine going through all the phases of clinical trials, and then a field test with the RTS,S vaccine,” she said.
The R21/Matrix M, she said, “can be an additional tool to join the vaccine that has been found to have a reasonable level of efficacy, the RTS,S vaccine, in reducing severe malaria and deaths in children.”
Only three months ago, the Gates Foundation said it was withdrawing financial support from the rollout of the RTS,S vaccine because of its low efficacy ratings, and would prioritize its investments in classical measures like insecticide treated bednets.
The RTS,S vaccine, the first ever to be approved by WHO in October 2021, was piloted among some 800,000 infants and children, demonstrating a 40% reduction in malaria episodes and a 31% reduction in severe malaria infections in a three country pilot.
The WHO later said it would spend US$160 million to roll out the vaccine more widely between now and 2025, beginning in Ghana, Kenya and Malawi.
‘Aimed at licensing this vaccine for widespread use next year’
But if the results of the R21/Matrix-M hold up in a Phase 3 trial – which researchers hope will yield sufficient results for licensing by next year – this newer vaccine could very well supercede the other vaccine, upending WHO’s original plans.
In their findings reported in The Lancet Infectious Diseases, researchers from the University of Oxford and their partners found that a vaccine booster dose at one year following a primary three-dose regime, had an efficacy of at least 75% in preventing malaria episodes – as compared to about 40% for the WHO-approved RTS,S vaccine.
This higher efficacy also meets the WHO’s Malaria Vaccine Technology Roadmap goal – once considered largely aspirational. The R21/Matrix-M vaccine had previously demonstrated efficacy of 77% over the first 12 months of the randomized, controlled vaccine trial involving a total of 450 participants aged five to 17 months, recruited in the region of Nanoro, Burkina Faso.
In the most recent study of a booster dose of the R21/Matrix-M, some 409 of the original 450 participants returned to receive the booster after a year, leading to a similar outcome. The trial is continuing for another two years to assess both potential value of additional booster vaccine doses, and longer-term safety.
Halidou Tinto, a professor in parasitology and the trial’s principal investigator, said it is “fantastic to see such high efficacy again after a single booster dose of vaccine. We are currently part of a very large Phase III trial aimed at licensing this vaccine for widespread use next year.”
Adrian Hill, a co-author of the paper who is a professor of vaccinology and director of the University of Oxford’s Jenner Institute, also expressed delight “to find that a standard four-dose immunization regime can now, for the first time, reach the high efficacy level over two years that has been an aspirational target for malaria vaccines for so many years.”
Mechanism of action
R21/Matrix-M is a pre-erythrocytic malaria vaccine candidate developed by scientists at the University of Oxford and manufactured by the Serum Institute of India.
It is produced by expressing recombinant Hepatitis surface antigen virus-like particles in Hansenula polymorpha, a microorganism that occurs naturally in some insects and food. The trial was funded by the EDCTP2 programme, supported by the European Union, Wellcome Trust and NIHR Oxford Biomedical Research Centre.
RTS,S, a recombinant protein-based malaria vaccine, aims to trigger the immune system to defend against the first stages of malaria when the Plasmodium falciparum parasite enters the human host’s bloodstream through a mosquito bite and infects liver cells.
The vaccine is designed to prevent the parasite from infecting the liver, where it can mature, multiply, re-enter the bloodstream, and infect red blood cells, which can lead to disease symptoms.
It resulted from 30 years of research and development by GSK and through a partnership with PATH, with support from a network of African research centres. The Bill and Melinda Gates Foundation provided catalytic funding for late-stage development of RTS,S between 2001 and 2015, according to WHO.