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expert reaction to phase 3 results of the R21/Matrix-M malaria vaccine candidate in African Children

A study published in The Lancet looks at the results of the malaria R21/Matrix-M vaccine. 


Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said:

“It is really encouraging to see an efficacy of 68–75% with R21.  It is early days, in the sense that the follow up has been quite short so far, as it is an ongoing trial and that the trial is limited geographically to effectively two regions in Africa.  The data shows a slightly lower efficacy in in regions with continuous malaria transmission and there is a tendency to weaning off the effect at the 12 month period, which is a bit concerning.  So there is eager expectation to see the longer term activity of the vaccine and the level of protection in wider areas in Africa and world-wide.”


Prof Eleanor Riley, Professor Emerita in Immunology and Infectious Disease, University of Edinburgh, said:

“This is a high quality randomised, placebo-controlled, clinical trial conducted by a highly experienced team.  The study was conducted over five different sites in East and West Africa.  The sites were chosen to represent situations where malaria occurs in a short, sharp burst during and after a similarly short, sharp rainy season (seasonal transmission) or where malaria cases can occur at any time during the year due to extended periods of wet weather (standard transmission).

“The R21 vaccine is, in essence, a re-engineered version of the existing RTS,S vaccine developed by GSK.  R21 benefits, however, from having a higher ratio of malaria antigen to carrier protein and is combined with a modified adjuvant.  This may explain the apparently higher immunogenicity of R21 compared to RTS,S but as the two vaccines have not been tested against each other in head-to-head studies it is not possible to directly compare the two vaccines.  R21 seems to be able to be manufactured at larger scale (and lower cost) than is currently the case for RTS,S.

“Overall, vaccine efficacy (against a clinical episode of malaria in the year after vaccination) was high (60-80%) and in line with data from previous, smaller studies of this vaccine.

“Interestingly, the vaccine also seems to offer approx. 50% protection (over the same time frame) against asymptomatic carriage of malaria parasites.  This is potentially important as asymptomatic malaria infections can predispose children to anaemia and other serious infections, and can also provide a source of malaria infection for mosquitoes, leading to sustained malaria transmission.  If confirmed in larger, population-wide studies, this reduction in asymptomatic infections could have significant public health benefits beyond individual protection against acute malaria episodes.

“The highest efficacy against clinical disease was seen in the seasonal transmission sites where the vast majority of infections occurred within the first 150 days after immunisation (see Figure 2a – the lines climb steadily for 150 days and then flatten off, indicating no new cases).  It is therefore not possible to say from this study whether the vaccine would continue to provide high levels of protection during the next year’s malaria season.  However, even if protection wanes from one year to the next, it would be possible to give children annual boosters until they reach an age when the risk of disease begins to fall.

“Vaccine efficacy was lower (but still high) in the standard sites with perennial malaria transmission.  This was despite the overall intensity of malaria transmission being lower in these sites than in the sites with seasonal transmission (fewer of the control children experienced one or more episodes of infection in the standard sites than in the seasonal sites).  In sites with perennial transmission, most of the infections occurred more than 150 days after immunisation but the rate of infection was then pretty consistent over the next 150 days (this is evident from the change in the slope of the lines in Figure 2b with an increase in the slope after 150 days).  This suggests that the vaccine continues to protect for up to 300 days but at a somewhat lower level than in the first 150 days.  This is reflected in the author’s own analysis of waning vaccine efficacy over time.

“Overall, the study confirms that R21 is safe and effective.  Its high (albeit potentially not hugely long-lived) efficacy, combined with its likely ready availability, suggests that it could play a very important role (in combination with other malaria control measures such as insecticide treated bed nets and antimalarial drugs) in reducing the burden of malaria in children in areas of seasonal or low to moderate perennial transmission.

“There is however, one important caveat.  None of the five sites in the study represents an area of intense, perennial malaria transmission such as is seen – for example – in central Africa.  This is the ultimate test of any malaria vaccine.”




‘Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, doubleblind, randomised, phase 3 trial’ by Mehreen S Datoo et al. was published in the Lancet at 23:30 UK time on Thursday 1 February 2024.

DOI: 10.1016/S0140-6736(23)02511-4



Declared interests

Dr Alena Pance: “I have no vested interests regarding this study and therefore no conflict of interest in my comments.”

Prof Eleanor Riley: “EMR has previously been involved in clinical trials of the GSK RTS,S vaccine.”


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