“R21/Matrix-M Malaria Vaccine: Potential Impact and Rollout”

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Malaria overview

Malaria (malaria), caused by P. falciparum y P. vivaxIt’s a terrible disease. In 2021 is estimated to have produced:

• More than 247 million cases and 619·000 deaths.
• In the African continent there are 95% of cases and 96% of deaths.
• Children under 5 years of age suffer at least 80% of malaria deaths on the African continent.

The RTS,S/AS01e (RTS,S: Mosquirix, GSK) vaccine is the first WHO-approved malaria vaccine. This step took place in October 2021 and in 2023 the last steps are taken for its large-scale launch in countries with moderate/high transmission of the parasite infection. P. falciparum.

another vaccine, R21/Matrix-Mdeveloped by the University of Oxford in collaboration with Novavax and to be manufactured by the Serum Institute of India (SII), is about to join the arsenal and complement the expected impact of RTS,S.

This new vaccine, R21/Matrix-M, already has been approved in Ghana, thus being the first country to approve this vaccine against malaria. It is estimated that this disease kills a child every minute in the world and in Ghana itself there were 5.3 million cases and 12·500 deaths in 2021. Data from a phase 2 study with R21/Matrix-M have been published (Datoo MS, Lancet Infect Dis 2022) and it is expected to know very soon those of phase 3 already finished.

Despite the absence of malaria vaccines to date, between 2000 and 2015 significant progress was made in reducing infections and deaths through vector control and the use of antimalarials, to the point of even dreaming of their elimination. However, since 2015 progress has slowed, and this has been markedly worsened by the COVID-19 pandemic. Now the hope is that the use of various vaccines, along with other approaches to reduce infection, will radically change the global picture of this disease.

Some details of this vaccine are shown in this note from Gavi documents (The Vaccine Alliance). In a previous note some aspects of the RTS,S/AS01e (Mosquirix) vaccine, already approved and about to be distributed on a large scale, have been commented.

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Early reports show that the R21/Matrix-M vaccine could have a significant impact

Although phase 3 data for this vaccine have not yet been published and are expected soon, phase 2 data have shown high efficacy after a fourth booster dose (Datoo MS, Lancet Infect Dis 2022). Unpublished phase 3 data show similar vaccine performance to the phase 2 trial, according to Adrian Hill of the Jenner Institute at the University of Oxford.

Las Ghanaian authorities have evaluated the data from this trial and approved the vaccine for use in children 5 to 36 months, who are most at risk of death from malaria.

This new vaccine comes immediately after the RTS,S vaccine, which was approved in October 2021 by the WHO. Four doses of this vaccine reduce cases of clinical malaria by 39% and severe disease by 30%. Given the extreme burden that malaria places on families, communities and economies in affected countries, this is not insignificant, and the vaccine has already been given to one million children in pilot campaigns since 2019. A new, second vaccine effective, it could transform, improve even more, the panorama of malaria in the world.

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The vaccine targets the first stage of the parasite’s life cycle.

when the mosquito Anopheles, that carries the malaria parasite, bites a person, introduces the parasite into their bloodstream, where it changes form through the stages of its life cycle. The complexity of this cycle has been the main barrier to vaccine development for many years. The R21/Matrix-M vaccine targets the sporozoite, which is the first form of the parasite once it enters the human body.

Infected mosquitoes inject only a few (10 to 100) sporozoites before the parasite multiplies, making them an ideal target for a vaccine. R21/Matrix-M is a subunit vaccine that contains parts of a protein secreted by the sporozoite, which bind to a component of the hepatitis B virus known to trigger a strong immune response.

The vaccine also contains Matrix-M (Novavax), an adjuvant that enhances the immune response. This technology, which has been used in the Novavax (Nuvaxovid) COVID-19 vaccine, induces the arrival of antigen-presenting cells at the injection site and enhances antigen presentation in local lymph nodes, meaning that the immune system is activated as strongly as possible.

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Vaccine rollout could begin as soon as WHO gives the go-ahead

Formal results from the ongoing Phase 3 trial involving 4,800 children in Burkina Faso, Kenya, Mali, and Tanzania are expected to be published later this year (NCT04704830). The WHO is currently evaluating the available data and is pending a decision on whether to prequalify the vaccine for wider use. If approved by the WHO, Gavi and UNICEF could start financing and procuring doses immediately to protect children on the African continent as soon as possible. In addition, the idea, for the moment, is not to replace the RTS,S vaccine but to be a complementary tool.

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Supply must be able to meet demand

The Oxford University team has an agreement with the Serum Institute of India to produce up to 200 million doses a year, which will mean the vaccine will not suffer the same manufacturing bottlenecks as many other vaccines. This is critical because vaccinating people at high risk of malaria simultaneously will be important in stopping the spread of the disease, as well as protecting the vaccinated and unvaccinated.

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Technology transfer could mean local production in Ghana

Serum Institute of India has announced a technology transfer agreement to produce the vaccine in Ghana. This can start as soon as the construction of a manufacturing facility in Accra, the capital of Ghana, is completed.

The COVID-19 pandemic has made it abundantly clear that relying on vaccine production in a few countries that then send the doses to where they are needed is fraught with potential problems and is often more expensive on top of that. Countries like Brazil and India already have strong manufacturing capacity, but building local vaccine production capacity in Africa is critical.

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More information on this website

Bibliographic references and recommended links

• Datoo MS, et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. Lancet Infect Dis. 2022;22(12):1728-36.
• Gavi, November 2022. Expanding sustainable vaccine manufacturing in Africa: Priorities for Support. Delivered by Gavi and partners in response to a call from the African Union and G7 Development Ministers.
• Geddes L. Malaria vaccines are finally ready for action: what happens next? Gavi, April 25, 2023.
• Geddes L. The groundbreaking history of the world’s first malaria vaccine. Malaria occupies a unique place in human history. Gavi, December 3, 2021.
• WHO, March 29, 2023. Fact sheets. Malaria.
• WHO, April 25, 2023. WHO urges increased implementation of recommended tools to combat malaria.
• WHO, March 2, 2020. Malaria: The malaria vaccine implementation programme (MVIP).
• University of Oxford, April 13, 2023. R21/Matrix-M™ malaria vaccine developed by University of Oxford receives regulatory clearance for use in Ghana.
• University of Oxford, September 8, 2022. Malaria booster vaccine shows durable high efficacy in African children, meeting WHO-specified 75% efficacy goal.

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