Trial Shows Malaria Vaccine Protects Young Children

Malaria clinic in Cameroon (U.S. Embassy Yaoundé)

23 Apr. 2021. Results from a clinical trial in Burkina Faso show a high efficacy rate for a candidate vaccine to protect young children against malaria infections. Findings from the trial testing a vaccine developed by the Jenner Institute at University of Oxford in the U.K. with an adjuvant made by biotechnology company Novavax Inc. in Gaithersburg, Maryland appear this week in a non-peer reviewed preprint on The Lancet web site.

Malaria, according to World Health Organization, affected 216 million people in 2016, which extracts heavy social and economic burdens in developing countries. In 2016, some 445,000 people died from malaria, of which 90 percent were in sub-Sahara Africa. Children under the age of 5 are particularly susceptible to the disease. The disease is caused by infections from the Plasmodium parasite transmitted by mosquitoes. In humans, the parasite multiplies in the liver, then infects red blood cells. Symptoms, including headache, fever, and vomiting, occur 10 to 15 days following transmission from a mosquito bite.

Researchers from the Jenner Institute and colleagues at Oxford developed a candidate vaccine code-named R21 to improve on another candidate vaccine called RTS,S/AS01. That vaccine, say the authors, shows limited efficacy in clinical trials so far, 56 percent over 12 months among children in Africa. For children age 5 to 17 months, the efficacy rate is 36 percent, with even lower rates, 18 to 26 percent, for younger children.

R21 is designed to act on Plasmodium parasites in the liver, early in the infection cycle before most symptoms appear. Like RTS,S/AS01, R21 is derived from a hepatitis B surface antigen that forms into virus-like particles in yeast. But unlike RTS,S/AS01, R21 limits the volume of hepatitis B surface antigen in the vaccine, which the authors say is associated with adverse effects. The R21 vaccine adds an adjuvant called Matrix-M, made by Novavax. Matrix-M is an additive that boosts immune responses, allowing for lower doses of the primary vaccine. The vaccine and adjuvant are licensed to Serum Institute of India for manufacturing.

Vaccine plus high or low dose of adjuvant

The Institute de Recherche en Sciences de Santé in Burkina Faso, in west Africa, conducted the mid-stage clinical trial through its Clinical Research Unit of Nanoro, a region of Burkina Faso. The researchers enrolled 450 children, age 5 to 17 months from 24 villages in the region. Participants were randomly assigned to receive three injections of the R21 vaccine, four weeks apart, with M21 adjuvants of 25 or 50 micrograms, or a rabies vaccine for comparison, before the malaria season. A fourth injection was given one year later. Comparison vaccines instead of a placebo indicate adverse reactions to vaccines in general, to better gauge adverse reactions to the malaria vaccine.

The study team looked primarily for malaria cases among participants in the six months following vaccination. Plus, researchers tracked duration of efficacy from the vaccine for 12 months, as well as adverse reactions for 28 days following injections, and antibody responses in the immune system.

After six months, 26 percent of children receiving R21 and the high-dose adjuvant, along with 30 percent of R21 and low-dose adjuvant recipients contracted malaria, compared to 71 percent of rabies vaccine recipients. Those percentages translate to vaccine efficacy rates of 77 percent for R21 plus high-dose adjuvant and 74 percent for low-dose adjuvant. Only a small number of adverse events were reported, mainly local site effects from the injections. Seven serious adverse effects among participants were reported, but were unrelated to the vaccine.

Halidou Tinto, director of the Clinical Research Unit of Nanoro and the trial’s principal investigator says in an Oxford statement that researchers “started recruitment for a Phase 3 licensure trial to assess large-scale safety and efficacy in 4,800 children, aged 5 to 36 months, across four African countries.” Adrian Hill, director of the Jenner Institute adds, “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 percent efficacy.”

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