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After decades of disappointing results, recent findings have revived hopes for an effective vaccine against malaria, which kills some 400,000 people every year, most of them children. An experimental vaccine that targets the most dangerous form of the malaria parasite was found to have an efficacy of 74% to 77% after 1 year in children from West Africa.
The results come from a small trial of a vaccine developed by researchers at the University of Oxford’s Jenner Institute involving 450 toddlers in Burkina Faso, where malaria is endemic.

“The efficacy we have got has never been obtained by any [malaria] vaccine candidate. These are really amazing findings,” says Halidou Tinto, a parasitologist at the Research Institute of Health Sciences in Nanoro, Burkina Faso, and a principal investigator at the site of the study. Its findings are in press at The Lancet and were posted 20 April on its preprint server.

Pedro Alonso, director of the World Health Organization (WHO) Global Malaria Programme, who was not involved with the work, calls it “very positive news.” But he adds: “This is a trial with 450 children. … We are still quite far away from having the type of information that would allow us to get very excited.”

The investigators are planning a pivotal phase 3 trial to launch later this year, enrolling 4800 children in Burkina Faso, Mali, Kenya, and Tanzania. In the best case, data from that trial could be submitted to regulators late in 2022 for approval in early 2023, says Oxford’s Adrian Hill, the trial’s chief investigator. He hopes that, if the phase 3 results support it, regulators will issue emergency use authorizations (EUAs) as they have for COVID-19 vaccines.

The children in the current trial, aged 5 months to 17 months, received three doses of vaccine at 4-week intervals and a booster dose at 12 months. Of the 146 children who received the vaccine along with a high dose of an immune-boosting compound called an adjuvant, 38 developed malaria, versus 105 of 147 children in a control group who received rabies vaccine. (That protocol ensured the control group also received value from being in the trial.)

The 77% efficacy against malaria dipped to 74% in children who received the malaria vaccine with a lower dose of adjuvant. The children’s levels of specific antibodies to malaria waned over 12 months, but the booster dose restored them.

WHO has called for the development of vaccines capable of reducing malaria cases by 75% by 2030. But the malaria parasite’s complex life cycle and shifting surface proteins have challenged vaccine developers. The highest efficacy previously published for a vaccine at 1 year after dosing was 56%, Hill notes. That was for Mosquirix, made by GlaxoSmithKline, which is structurally similar to the Oxford vaccine and also targets the parasite right after infection. Mosquirix is being deployed with WHO support in areas of Malawi, Kenya, and Ghana. (At 4 years out, that vaccine’s efficacy declined to 36%.) 

The Oxford vaccine, made in yeast, consists of hepatitis B surface protein combined with a piece of a protein that coats the surface of the malaria parasite when it first invades its human host. The hepatitis B surface proteins self-assemble into a “viruslike particle” studded with the malaria proteins.

The Oxford group has partnered with the Serum Institute of India, which is making vaccine for a planned phase 3 trial and has pledged to produce 200 million doses in the coming years; Hill says those doses can be manufactured cheaply.  “The price [will be] less per dose than anything ever before,” he says. The adjuvant, a purified plant compound called a saponin made by Novavax, is already being manufactured at scale as part of that company’s COVID-19 vaccine.

Others cautioned that many unknowns remain, and some called out what they called deficiencies in the Lancet preprint. “Where’s the biology?” asked Rhoel Dinglasan, who studies malaria at the University of Florida’s Emerging Pathogens Institute. He is developing a different malaria vaccine, aimed at stopping transmission of the parasite from humans to mosquitoes. He applauded the clinical results but wanted to see, among other things, genomic data from the malaria parasite that infected the vaccinated children.

Dinglasan says that without sequence data, it’s not clear whether the vaccine will be effective against all parasite strains. The efficacy of the GlaxoSmithKline malaria vaccine fell by one-third, to 33.4%, when there was a mismatch between a key part of the protein used in the vaccine and the corresponding protein in the parasite, he notes. And a mismatched vaccine could drive selection for vaccine-resistant parasites, potentially thwarting the quest for a highly effective vaccine once again.