The World Health Organization (WHO) announced its recommendation for the R21/Matrix-M vaccine for malaria prevention in children.
“The recommendation follows advice from the WHO: Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Group (MPAG) and was endorsed by the WHO Director-General following its regular biannual meeting held on 25-29 September,” the WHO stated Monday.
“The R21 vaccine is the second malaria vaccine recommended by WHO, following the RTS,S/AS01 vaccine, which received a WHO recommendation in 2021,” the WHO added.
The R21/Matrix-M vaccine was developed by the University of Oxford and manufactured by the Serum Institute of India.
It uses Novavax’s Matrix M adjuvant.
NEW: Oxford R21 malaria vaccine receives @WHO recommendation paving the way for global roll-out.
The vaccine developed by Oxford & @SerumInstIndia demonstrates a high efficacy.
The jab could reduce over half a million malaria-related deaths annually.#OxfordVaccine
— University of Oxford (@UniofOxford) October 2, 2023
“Almost exactly two years ago, WHO recommended the broad use of the world’s first malaria vaccine called RTS,S,” WHO chief Tedros Adhanom Ghebreyesus said.
“Today, it gives me great pleasure to announce that WHO is recommending a second vaccine called R21/Matrix-M to prevent malaria in children at risk of the disease,” he added.
The Oxford malaria vaccine is expected to become available by mid-2024.
— World Health Organization (WHO) (@WHO) October 2, 2023
“WHO is now reviewing the vaccine for prequalification, which is WHO stamp of approval, and will enable GAVI (a global vaccine alliance) and UNICEF to buy the vaccine from manufacturers,” Tedros said.
20 MILLION DOSES
R21/Matrix-M is mass manufactured by Serum Institute of India and uses Novavax’s Matrix M adjuvant.
Adar Poonawalla, CEO of Serum Institute of India, said it had already produced more than 20 million doses in anticipation of WHO’s recommendation.
“We will ramp it up as per what the demand requirements are,” he said in an interview. “We hope that by the end of 2024, there will be zero mismatch of demand and supply, with our supply coming into the system.”
The vaccine will compete against the RTS,S shot by GSK Plc, which was recommended by the United Nations-agency in 2021 and sold under the brand Mosquirix.
The WHO said both vaccines had shown similar efficacy in separate trials, but without a head-to-head trial there was no evidence showing whether one performed better.Advertisement
Breaking: A cheap malaria vaccine that can be produced on a massive scale has been recommended for use by the World Health Organization.
The vaccine has been developed by the University of Oxford and is only the second malaria vaccine to be developed. https://t.co/SUADW9awFj
— BBC News Africa (@BBCAfrica) October 2, 2023
From the WHO:
Key features of the R21 malaria vaccine:
The updated WHO malaria vaccine recommendation is informed by evidence from an ongoing R21 vaccine clinical trial and other studies, which showed:
- High efficacy when given just before the high transmission season: In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to 4 or 5 months per year), the R21 vaccine was shown to reduce symptomatic cases of malaria by 75% during the 12 months following a 3-dose series. A fourth dose given a year after the third maintained efficacy. This high efficacy is similar to the efficacy demonstrated when RTS,S is given seasonally.
- Good efficacy when given in an age-based schedule: The vaccine showed good efficacy (66%) during the 12 months following the first 3 doses. A fourth dose a year after the third maintained efficacy.
- High impact: Mathematical modelling estimates indicate the public health impact of the R21 vaccine is expected to be high in a wide range of malaria transmission settings, including low transmission settings.
- Cost effectiveness: At prices of US$ 2 – US$ 4 per dose, the cost-effectiveness of the R21 vaccine would be comparable with other recommended malaria interventions and other childhood vaccines.
- Similarity of R21 and RTS,S vaccines: The two WHO-recommended vaccines, R21 and RTS,S, have not been tested in a head-to-head trial. There is no evidence to date showing one vaccine performs better than the other. The choice of product to be used in a country should be based on programmatic characteristics, vaccine supply, and vaccine affordability
- Safety: The R21 vaccine was shown to be safe in clinical trials. As with other new vaccines, safety monitoring will continue.
In a clinical trial conducted in Burkina Faso for the R21 malaria vaccine, “seven serious adverse events” occurred during a study including 450 children.
The researchers did not attribute any of the serious adverse events to the vaccine.
The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre funded the study.
A preprint paper titled “A Phase III Randomised Controlled Trial Evaluating the Malaria Vaccine Candidate R21/Matrix-M in African Children” read:
Background: Developing malaria vaccines has proved difficult with many challenges, including polymorphic antigens, modest field-trial efficacy, and now limitations on vaccine supply preventing widespread impact. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy against uncomplicated clinical malaria over 12 months in a licensure trial in African children. Recently, we found that a new R21 nanoparticle in the saponin adjuvant Matrix-M™ showed over 75% efficacy against a similar endpoint with seasonal administration in a phase IIb trial in Burkina Faso.
Methods: We report the results of a phase III trial of the R21/Matrix-M™ malaria vaccine in 4800 children across five sites in four African countries with differing malaria transmission intensities and seasonality. Children aged 5-36 months were included at all sites. Participants were randomised 2:1 to receive a 5µg dose of R21 in 50µg Matrix-M™ adjuvant or a control vaccine (licensed rabies vaccine). Vaccines were administered as three doses, four weeks apart, with a booster 12 months following the third dose. Half the children recruited were vaccinated at two sites with seasonal malaria transmission and the remainder at “standard” sites with perennial malaria transmission using year-round age-based immunisation. Evaluation of 12-month vaccine efficacy (VE) against clinical malaria was the primary endpoint. VE against multiple malaria episodes and severe malaria as well as safety and immunogenicity were also assessed. We report follow-up to 18 months at seasonal sites and 12 months at standard sites.This trial is registered on ClinicalTrials.gov, NCT04704830
Findings: The vaccine was well tolerated with injection site pain and fever as the most frequent local and systemic adverse events. A non-significant trend towards more febrile convulsions was observed in those who received R21/Matrix-M™ compared with rabies vaccines. There was no significant difference in the number of Adverse Events of Special Interest (AESIs) and Serious Adverse Events (SAEs) between the vaccine groups. Overall, 12 months VE was 75% (95% CI 71-79; p<0.001) at the seasonal sites and 68% (61-74; p<0.001) at the standard sites for time to first clinical malaria episode. VE against multiple clinical malaria episodes was similar: 75% (71-78; p<0.001) at the seasonal sites and 67% (59-73; p<0.001) at the standard sites. There was similar waning of efficacy over the first year of follow-up at both seasonal and standard sites. At the seasonal sites, a booster dose maintained efficacy to 18 months at the seasonal sites: VE was 74% (70-77; p<0.001) for time to first clinical malaria episode and 72% (68-75; p<0.001) against multiple clinical malaria episodes. Vaccine-induced antibodies against the conserved central NANP repeat sequence of the circumsporozoite protein correlated strongly with vaccine efficacy. Higher antibody titres were observed in the 5–17-month age group compared with 18–36-month-olds (p<0.0001). When compared with the older age group, the younger age group, in whom this vaccine is most likely to be deployed first, showed the highest 12-month vaccine efficacy on time to first clinical malaria episode at both seasonal, 79% (73-84, p<0.001), and standard sites, 75% (65-83, p<0.001).
That would make R21 the second WHO-approved vaccine for use against malaria. The first, called RTS,S or Mosquirix, was recommended for use in 2021 and has been given to 1.8 million children in Ghana, Malawi, and Kenya. Doses are expected to arrive in nine more countries in Africa by the end of the year. But the 18 million doses of that vaccine that are expected to be available between now and 2025 “are only about 10% of what we need” to protect the estimated 40 million children who are born every year in malaria-affected areas, says Matthew Laurens, a malaria vaccine expert at the University of Maryland School of Medicine. R21 could soon be available in much larger quantities.
Like RTS,S, R21 requires multiple initial doses and a later booster. Both vaccines induce immunity with a protein from the Plasmodium parasite that causes malaria. But the new vaccine contains a different immune-boosting agent, or adjuvant, which is somewhat easier to produce than the one used in RTS,S. The vaccine’s developers have already worked with the Serum Institute of India (SII), one of the world’s biggest vaccine makers, to manufacture R21. SII says it can produce more than 100 million doses of the vaccine per year. That would be “a leap forward” for efforts to fight malaria, Laurens says. “Having a second product would be fabulous.” And at an estimated price of less than $5 per dose, the new vaccine may be less expensive than RTS,S, which cost €9.30 per dose in the first major purchase of the vaccine by UNICEF.
In a paper published in The Lancet Infectious Diseases, a team of researchers warned about the dangers of the RTS,S malaria vaccine.
The researchers concluded that the findings in the malaria vaccine implementation programme (MVIP) “do not rule out the possibility of increased mortality among vaccinated girls compared with vaccinated boys, as observed in the phase 3 studies.”
“Three significant safety signals were identified, related to meningitis, cerebral malaria, and female-specific all-cause mortality,” the researchers noted.
The researchers concluded that the “claimed impact of the MVIP on mortality is not based on enough scientific evidence.”
The vaccine’s impact on severe malaria was estimated to be around 30%.
The paper’s final conclusions stated:
We have made several recommendations for the way forward (panel). Populations affected by malaria and their policy makers have waited for a vaccine for about half a century. The enthusiasm greeting the WHO recommendation of RTS,S is understandable. Unfortu-nately, the available data suggest that this vaccine, like some other non-live vaccines,16, 17 might increase all-cause mortality in girls to the extent that its deployment could lead to a net increase in deaths of girls among the recipients.