by University of Oxford

Credit: CDC

The results of a clinical trial into a new malaria vaccine candidate (RH5.1/Matrix-MTM) show it is well-tolerated and offers effective protection against the blood-stage of the disease—the first inoculation to do so.

Malaria, caused by Plasmodium falciparum parasites, is a leading cause of death in children under five in many parts of Africa. Blood-stage malaria—when the parasite infects red blood cells—causes symptoms of the disease like fever and chills, and can lead to severe, life-threatening complications such as anemia and organ failure.

The study has been run by scientists at the University of Oxford in collaboration with the Clinical Research Unit of Nanoro (CRUN) at the Institut de Recherche en Sciences de la Santé (IRSS) in Burkina Faso, the London School of Hygiene and Tropical Medicine (LSHTM) in the U.K. and the National Institute of Health (NIH) in the U.S., with support from other partners including the Serum Institute of India Pvt. Ltd, Novavax and ExpreS2ion Biotechnologies ApS.

The study team tested the safety and efficacy of the RH5.1/Matrix-MTM blood-stage malaria vaccine candidate in children aged 5 to 17 months in Nanoro Burkina Faso, following positive phase one results in Tanzanian adults and children.

More than 360 children were enrolled in the study in 2023 and divided into two groups: one received three doses of the RH5.1/Matrix-MTM and the other three doses of a rabies vaccine as control. Neither the participants, their families nor the study teams knew who received which vaccine.

The results, published in The Lancet Infectious Diseases, showed the vaccine was well tolerated with no safety concerns. Children who received the vaccine developed high levels of antibodies against the parasite, especially those who received their vaccine doses at 0, 1 and 5 months rather than at 0, 1 and 2 months. This group importantly achieved 55% effectiveness in preventing clinical malaria over a 6-month period.

In addition, within the group of children who did develop clinical malaria, a proportion showed very high levels of parasites in their blood. Notably, the vaccine also demonstrated more than 80% efficacy against these higher levels of malaria parasites, suggesting this vaccine could prevent severe cases of the disease in children in a real-world setting. These findings will now be explored further in future clinical trials.

Professor Angela Minassian, an infectious diseases physician and Associate Professor in The Department of Biochemistry who leads the clinical blood-stage malaria vaccine program at the University of Oxford, said, “Our goal, by targeting the blood-stage of the disease with this vaccine, is to significantly reduce the number of severe cases and deaths.

“The current licensed vaccines, R21/Matrix-MTM and RTS,S/AS01, target the liver-stage of the parasite and are very effective at stopping parasites from getting into the blood. However, if they fail and parasites slip through the net, disease will develop as these approved vaccines have no activity against malaria in the blood. Adding RH5.1/Matrix-MTM to these licensed vaccines should provide a vital second line of defense, achieving even higher levels of protection.

“Importantly, our study has provided the first real-world data to show that this type of vaccine works by reducing the level of parasites in the blood.”

Halidou Tinto, Professor of parasitology and Regional Director of the Institut de Recherche en Sciences de la Santé (IRSS), based in Burkina Faso said, “Frequent malaria infections can impair a child’s growth and development. Protecting against the blood-stage helps ensure children can grow up healthier and have better educational and developmental outcomes.

“This trial has shown that RH5.1/Matrix-MTM is safe and well-tolerated. No serious side effects were reported, and further stages of the trial and follow-on trials will continue to monitor the vaccine’s longer-term safety and efficacy.

“After the RTS,S/AS01 and R21/Matrix-MTM vaccines, we are proud to see the Clinical Research Unit of Nanoro again in the front of this good news for malaria endemic countries. More importantly, these amazing results open the door for a combined-vaccine approach with higher efficacy in the near future.”

Professor Simon Draper, Professor of Vaccinology and Translational Medicine in the Departments of Pediatrics and Biochemistry, the Kavli Institute of Nanoscience, and inventor of the RH5.1/ Matrix-MTM vaccine said, “The development of an effective blood-stage malaria vaccine has proved to be an exceptionally tough scientific challenge, with previous clinical trials over a number of decades reporting no or minimal efficacy.

“These first efficacy results for a new generation of blood-stage vaccine candidates targeting the RH5 malaria protein are hugely encouraging, and represent a major milestone for the malaria field.

“We now have the exciting opportunity to test the new RH5.1 blood-stage vaccine in combination with the approved liver-stage vaccines, with the goal of developing a second-generation product that can offer very high-level efficacy against malaria disease in young African children.”

This was a double-blind, randomized, controlled phase 2b trial. Novavax’s saponin-based Matrix-M adjuvant, which enhances the immune system response and increases the magnitude and durability of the antibody response, is used for both the RH5.1/Matrix-M vaccine candidate and R21/Matrix-M vaccine.

More information: Hamtandi M Natama et al, Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children, The Lancet Infectious Diseases (2024). DOI: 10.1016/S1473-3099(24)00752-7

Journal information:Lancet Infectious Diseases

Provided by University of Oxford

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