R21/Matrix-M™ Malaria Vaccine Clinical Trials, Dosage, Efficacy, Side Effects, Usage
The R21/Matrix-M™ vaccine includes Novavax AB proprietary saponin-based Matrix-M adjuvant and is licensed to and manufactured by the Serum Institute of India Private Ltd (SII). R21/Matrix-M was designed to improve the RTS, S/AS01 malaria vaccine. The University of Oxford Jenner Institute created R21. 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 Novavax AB 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.
On October 2, 2023, the World Health Organization (WHO) recommended R21/Matrix-M to prevent malaria in children. The recommendation follows advice from the WHO's Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Group (MPAG). The R21 vaccine reduced symptomatic malaria cases by 75% during the 12 months following a 3-dose series. The WHO says a fourth dose given a year after the third maintained Efficacy. On December 21, 2023, the WHO added the R21/Matrix-M malaria vaccine to its list of prequalified vaccines, a prerequisite for vaccine procurement by UNICEF and funding support for deployment by Gavi, the Vaccine Alliance.
A perspective paper published by the Malaria Journal on January 12, 2024, examined the R21/Matrix-M malaria vaccine, its development, potential impact on global malaria eradication efforts, and the challenges and opportunities it presents. On February 1, 2024, The Lancet published results from a phase 3 study that conducted R21/Matrix-M, which was well tolerated and offered high efficacy against clinical malaria in African children. The Lancet reported on February 3, 2024, that over 3 million children in 20 countries will receive malaria vaccination in 2024.
John Jacobs, Novavax Inc.'s President and CEO, said in a press release on July 15, 2024, "The introduction of the R21/Matrix-M™ malaria vaccine in Côte d'Ivoire marks a breakthrough in the fight to protect vulnerable children against a leading cause of death across the region while reinforcing our mission to create innovative vaccines that improve public health."
On October 31, 2024, TIME awarded the R21/Matrix-M™ malaria vaccine a 'Best Inventions of 2024.'
Oxford University's Jenner Institute is within the Nuffield Department of Medicine, located at the Old Road Campus Research Building in Headington, Oxford. Serum Institute of India Pvt. Ltd. is a significant vaccine manufacturer by the number of doses produced and sold globally (more than 1.5 billion doses), which includes Polio vaccine, Diphtheria, Tetanus, Pertussis, Hib, BCG, r-Hepatitis B, Measles, Mumps, Rubella as well as Pneumococcal and Covid-19 vaccines. The Poonawalla Bio-Tech Park at Manjari in Pune, India, is over 42 acres.
R21/Matrix-M Vaccine Efficacy
The Lancet published results from a Phase 3 efficacy trial of the R21/Matrix-M™ malaria vaccine on February 1, 2024. The publication reported Efficacy of 75% when administered before the high transmission season: In areas with highly seasonal malaria transmission (where malaria transmission is mainly limited to 4 or 5 months per year), the R21/Matrix-M vaccine was shown to reduce symptomatic cases of malaria by 75% during the 12 months following a 3-dose series. Efficacy of 68% when administered in an age-based schedule in regions where malaria is present perennially during the 12 months following the first three doses. On September 26, 2023, a Phase III Randomised Controlled Trial concluded that R21/Matrix-M™ has a well-tolerated safety profile and offers high-level Efficacy against clinical malaria in African children at seasonal and perennial transmission sites.
Matrix-M Commercial Agreements
Serum Institute (SII) has the commercial rights to use Novavax Inc. Matrix-M in the vaccine and pay Novavax royalties. Additionally, Novavax has the commercial rights to sell and distribute the SII-manufactured malaria vaccine in certain countries and military vaccine markets.
R21/Matrix-M Vaccine Availability 2024
As of October 2024, Nigeria, Mozambique, South Sudan, DR Congo, Central African Republic, Kenya, Cameroon, Chad, Malawi, Benin, and Côte d'Ivoire received R21 vaccines. The Food and Drugs Authority of the Republic of Ghana licensed the R21/Matrix-MTM malaria vaccine on April 13, 2023. Nigeria issued its authorization on April 17, 2023. On July 24, 2023, Burkina Faso's Agence Nationale de la Regulation Pharmaceutique approved using R21. Previously, 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.
R21.Marrix-M Vaccine Production
As of April 2024, the Serum Institute of India manufactured about 25 million R21/Matrix-M vaccine doses. On October 12, 2023, UNICEF announced an agreement to secure supplies of R21/Matrix-M.
R21/Matrix-M Indication
The R21/Matrix-M Malaria Vaccine is indicated to prevent Plasmodium falciparum malaria, a mosquito-borne disease. The vaccine has been approved for use in certain countries in children aged 5 to 36 months. There were 229 million malaria cases worldwide in 2019, with an estimated 409,000 deaths. According to the 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 Dosage
R21/Matrix-M Malaria vaccine is offered as a three or four-dose primary regime.
R21/Matrix-M Side Effects
In a phase 3 clinical trial, the most common adverse events with the vaccine were fever (47%) and injection site pain (19%).
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 high volumes. The SIIPL has established a production capacity for 100 million doses per annum.
Matrix-M™ Adjuvant
Novavax Inc.'s Matrix-M adjuvant comes from saponins, naturally occurring compounds in the bark of the Quillaja saponaria tree. Saponins have a long history of being used for their medicinal properties.
R21/Matrix-M Vaccine Cost Effectiveness
The WHO stated that at prices of $2 – $4 per dose, the cost-effectiveness of the R21 vaccine would be comparable with other recommended malaria interventions and other childhood vaccines.
R21/Matrix-M Vaccine News
October 17, 2024 - Nirgeria's Federal Government took delivery of one million doses of the R21/Matrix-M malaria vaccine donated by Gavi, the Vaccine Alliance.
July 16, 2024 - “The nationwide rollout of the malaria vaccine marks a significant milestone in South Sudan's journey to reduce the devastating burden of malaria and save countless young lives..... ,” said Patience Musanhu, Gavi Senior Country Manager for South Sudan.
July 15, 2024 - Professor Adrian Hill, Director of the Jenner Institute at Oxford University, said in a press release: “The (Côte d'Ivoire) rollout of the R21/Matrix-M™ malaria vaccine marks the start of a new era in malaria control interventions with the high efficacy vaccine now accessible at a modest price and very large scale to many countries in greatest need. We hope this vaccine can be provided to all African countries who wish to use it very soon.”
May 23, 2024 - Dr. Sania Nishtar, CEO of Gavi, the Vaccine Alliance, stated, "That is what matters most – that countries where our vaccines can be most impactful can access them, saving thousands of lives each year and offering relief to families, communities and entire health systems."
February 1, 2024 - Article: Safety and Efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomized, phase 3 trial. Professor Adrian Hill, the chief investigator of the R21/Matrix-M™ phase 3 trial, said, "The continued high Efficacy of this new vaccine in field trials is very encouraging and consistent with the high Efficacy and excellent durability observed in a smaller four-year phase IIb trial. These data support an important role for the unique high-density nanoparticle display of the conserved repeat region of the malaria parasite circumsporozoite protein, a feature in the design of the R21 vaccine, in providing such high vaccine efficacy and, thereby, an important new tool for malaria control".
December 21, 2023 - Dr. Kate O'Brien, Director of WHO's Department of Immunization, Vaccines, and Biologicals, commented: "Today marks a huge stride in global health as we welcome the prequalification of R21/Matrix-M, the second malaria vaccine recommended for children in malaria-endemic areas.
December 13, 2023—The journal Nature published an article titled "Malaria fighter: this researcher paved the way for a game-changing vaccine."
April 13, 2023 - GAVI reported: Five things you need to know about the new R21 malaria vaccine.
December 1—022 - 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.
September 7, 2022 - The peer-reviewed 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. In children who received R21 with the higher dose of Matrix-M adjuvant, Efficacy was 80% at 12 months following the booster vaccination.
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, which Novavax produces.
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 immunogenic in African children and demonstrates promising high-level Efficacy.
May 7, 2015 - A vaccine against malaria developed at Oxford University's Institute has shown promising results in its first field trial. The results are published 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.
Phase 3 (NCT04704830) Clinical Study Interpretation: R21/Matrix-M™ has a well-tolerated safety profile and offers high-level Efficacy against clinical malaria in African children at seasonal and perennial transmission sites. This low-cost vaccine, soon to be available at over 100 million doses a year and already licensed in three African countries (Burkina Faso, Ghana & Nigeria), could substantially contribute to reducing the burden of malaria disease and deaths in sub-Saharan Africa. Funding: The Serum Institute of India Pvt. Ltd, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.
The Phase1/2 trial was funded by the EDCTP2 program supported by the European Union (grant number RIA2016V-1649-MMVC), the Wellcome Trust, and the NIHR Oxford Biomedical Research Centre. Oxford researchers and their partners reported from a Phase IIb trial that a booster dose of R21/Matrix-M at one year following a primary three-dose regime maintained high Efficacy against malaria and continued to meet the World Health Organization Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy. This followed 2021 results from the Phase-IIb trial reporting that R21/Matrix-M demonstrated a high-level efficacy of 77%. Recent data from the significant phase III trial also show high levels of effectiveness and a reassuring safety profile.
A Phase 3 trial assesses large-scale safety and Efficacy in 4,800 children 5-36 months across Burkina Faso, Kenya, Mali, and Tanzania.
