R21/Matrix-M™ Malaria Vaccine
The R21/Matrix-M™ vaccine was created by the University of Oxford and includes Novavax AB proprietary saponin-based Matrix-M adjuvant and is licensed to and manufactured by the Serum Institute of India Private Ltd (SII). The R21 was created by the University of Oxford Jenner Institute, located in England. In 2017, Oxford published an abstract: High-level efficacy in humans of a next-generation plasmodium falciparum anti-sporozoite vaccine: R21 in Matrix-M adjuvant.
R21/Matrix-M is produced by expressing recombinant HBsAg virus-like particles in Hansenula polymorpha, comprising the central repeat and the C-terminus of the circumsporozoite protein (CSP) fused to the N-terminal end of HBsAg10.
Under Novavax's agreement with Serum Institute (SII), it has the commercial rights to use Matrix-M in the vaccine in regions where the disease is endemic and pay Novavax royalties. Additionally, Novavax has the commercial rights to sell and distribute the SII-manufactured vaccine in certain countries, primarily in the travelers' and military vaccine markets.
On April 20, 2021, Adrian Hill, Director of the Jenner Institute and Lakshmi Mittal and Family Professor of Vaccinology at the University of Oxford, and co-author of a non-peer-reviewed paper, said in a press release, 'These new results support our high expectations for the potential of this vaccine, which we believe is the first to reach the WHO's goal of a vaccine for malaria with at least 75% efficacy. The Phase 2b clinical trial targeted children 5-17 months.'
On September 7, 2022, The Lancet Infectious Diseases published: Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after two years follow-up in children in Burkina Faso: a phase 1/2b randomized controlled trial, that concluded - A booster dose of R21/Matrix-M at one year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine-induced antibody concentrations correlated with vaccine efficacy.
Oxford University: ground-breaking research and innovation. The Jenner Institute is based within the Nuffield Department of Medicine, University of Oxford, and operates out of the Old Road Campus Research Building in Headington, Oxford.
The Drugs Controller General of India granted permission on September 29, 2022, to send two lakh doses of the R21/Matrix-M vaccine manufactured by Serum Institute to the UK.
On December 19, 2022, the journal Nature published an article: After 30 years of development, there is finally a vaccine for malaria. But it might take years to get it to the children who need it.
R21/Matrix-M Malaria Vaccine is indicated to prevent Plasmodium falciparum malaria, a mosquito-borne disease. There were 229 million malaria cases worldwide in 2019, with an estimated 409,000 deaths. According to the World Health Organization (WHO), children under five are the most vulnerable, accounting for 67% of malaria-related fatalities worldwide in 2019.
On December 8, 2022, the WHO published the World Malaria Report 2022, which offers in-depth information on the latest malaria control and elimination trends at global, regional, and country levels.
R21/Matrix-M Malaria vaccine three-dose primary regime dosage was tested in the Phase 2b clinical trial. Participants aged 5-17 months received 5 mg of R21 with either 25 mg or 50 mg of Matrix-M or a rabies vaccine as a control.
R21/Matrix-M Booster Dose
This phase 1/2b randomized controlled clinical trial reports the safety, immunogenicity, and efficacy of the R21/Matrix-M malaria vaccine. The administration of a booster dose 12 months following the 3-dose primary series of R21/Matrix-M vaccinations shows the added benefit of a fourth dose when administered before the malaria season. Vaccine efficacy was maintained in the high-dose adjuvant group, at 80% following the booster vaccine over 12 months and 75% over 24 months after the prior three-dose regimen. Furthermore, vaccine efficacy against multiple episodes of clinical malaria was similar (78%) over two years of follow-up. R21/Matrix-M has a favorable safety profile and induces high levels of malaria-specific anti-NANP antibodies that correlate with the observed protection against clinical malaria.
R21/Matrix-M Vaccine Manufacturing
The University of Oxford has partnered with Serum Institute of India Pvt Ltd. (SIIPL) to manufacture R21/Matrix-M to ensure the provision of low high volumes of low-cost vaccines and access in countries where it is required the most. SIIPL has confirmed its commitment to providing about 200 million doses annually after licensure.
R21/Matrix-M Vaccine News
December 1, 2022 - The Lancet Infectious Disease published: Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after two years follow-up in children in Burkina Faso: a phase 1/2b randomized controlled trial.
November 3, 2022 - MedpageToday reported the malaria vaccine candidate demonstrated an overall efficacy of 75% in children with no serious safety concerns.
September 29, 2022 - The WHO launches a new initiative to stop the spread of invasive malaria vectors in Africa.
September 8, 2022 - Professor Adrian Hill, the University of Oxford's Director of the Jenner Institute, Lakshmi Mittal and Family Professor of Vaccinology, and co-author of the research paper, said: 'We are delighted 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.'
September 7, 2022 - The peer-review journal The Lancet published the findings from a booster dose clinical trial - These findings show that R21/Matrix-M has again reached the WHO-specified efficacy goal of 75% or greater over 24 months in the target population of African children. And in children who received R21 with the higher dose of Matrix-M adjuvant, efficacy was 80% at 12 months following the booster vaccination.
July 22, 2022 - A multidisciplinary approach to eradicating malaria
April 25, 2022 - Sheikh Mohamed bin Zayed, Crown Prince of Abu Dhabi, said that UAE is committed to eliminating malaria.
April 22, 2022 - "We are finally nearly at the finish line. It's exciting," Adrian Hill, the institute's director, said in northern Tanzania on a visit to field trials of the R21/Matrix-M jab.
May 10, 2021 - National Geographic article: At last, a malaria vaccine has passed critical clinical trials.
May 5, 2021 - The Lancet published an editorial: R21/Matrix-M: a second malaria vaccine?
May 4, 2021 - News article: Explained: Why a malaria vaccine candidate has raised new hope and what went into its making.
April 30, 2021 - BMC article: The new vaccine, R21, is very similar to RTS,S/AS01, in that it still contains the central repeat and the C-terminus of the circumsporozoite protein (CSP) fused to the N-terminal end of HBsAg. However, in contrast with RTS,S/AS01, does not contain the HBsAg in monomer form, only as fusion protein moieties, providing more surface for the CSP on the virus-like particle, making for a more specific immune response. In addition, R21 is mixed with a different saponin-based adjuvant called Matrix-M, produced by Novavax. The vaccines used in the trial were made at the Serum Institute of India, the world's largest vaccine producer.
April 23, 2021 - A pre-print publication of data from a Phase 2b clinical trial in children demonstrating 77 percent efficacy for a malaria vaccine candidate, R21, created by the University of Oxford that includes Novavax's Matrix-M™ adjuvant and is licensed to Serum Institute of India (SII). The Phase 2b randomized, controlled, double-blind trial was conducted at the Clinical Research Unit of Nanoro / Institut de Recherche en Sciences de la Santé (IRSS), Burkina Faso, and recruited 450 participants from the catchment area of Nanoro, a setting with highly seasonal malaria transmission.
April 20, 2021 - The Lancet published a non-peer-reviewed study: High Efficacy of a Low Dose Candidate Malaria Vaccine, R21 in 1 Adjuvant Matrix-M™, with Seasonal Administration to Children in Burkina Faso. Interpretation: R21/Matrix-M appears safe and very immunogenic in African children and demonstrates promising high-level efficacy.
May 7, 2015 - A vaccine against Malaria developed at Oxford University's Jenner Institute has shown promising results in its first field trial. The results are published today in the journal Science Translational Medicine.
R21 / Matrix-M Malaria Vaccine Clinical Trials
R21/Matrix-M Malaria Vaccine candidate continues progressing through the Clinical Trial process.
The Phase1/2 trial was funded by the EDCTP2 program supported by the European Union (grant number RIA2016V-1649-MMVC) and the Wellcome Trust and NIHR Oxford Biomedical Research Centre. It was extended for another two years to assess if further booster doses would be necessary to maintain high efficacy over time. The Phase IIb randomized, double-blind trial was conducted at the Clinical Research Unit of Nanoro / Institut de Recherche en Sciences de la Santé, Burkina Faso. A total of 450 participants aged five to 17 months were recruited from the catchment area of Nanoro, with 409 receiving the booster.
A Phase 3 trial assesses large-scale safety and efficacy in 4,800 children 5-36 months across four African Countries. Results from the Phase III licensure trial are expected in 2022.