A small clinical trial testing a vaccine against malaria has shown promising results, and for the first time, appears to have met the World Health Organization’s target efficacy benchmark, Heidi Ledford reports for Nature News.
Malaria kills about 400,000 people per year, mostly young children, so scientists have spent decades attempting to develop a strong vaccine. The World Health Organization called on the scientific community in 2013 to develop and license a vaccine that is at least 75 percent effective by 2030. The results of the latest trial show that a high dose of the experimental malaria vaccine has a 77 percent efficacy rate at preventing malaria infections over the course of one year. The results were published report last week in the Lancet's preprint server, so the findings have not yet been externally peer-reviewed.
“The efficacy we have got has never been obtained by any [malaria] vaccine candidate. These are really amazing findings,” says Nanoro Institute for Health Sciences Research parasitologist Halidou Tinto, a lead investigator of the new study, to Meredith Wadman at Science magazine.
The trial involved 450 children between five and 17 months old, split into three groups: a high dose of vaccine, a lower dose of vaccine, which resulted in a 71 percent efficacy rate, and a group that received a licensed rabies vaccine instead of the trial malaria vaccine. That way, all participants benefited from involvement with the study, reports Science magazine.
The research team also plans to continue administering booster shots and following the 450 participants for at least another year or two, Tinto tells Nature News. The researchers are also now planning a Phase III trial with 4,800 children, aged five months to three years old, across four African countries.
If the efficacy rate holds up to further trials, the Oxford University vaccine, called R21, will be far more effective than any previously tested vaccine. The second-most effective malaria vaccine, called Mosquirix, is about 56 percent effective over one year, and that falls to 36 percent effective over four years, per Nature News.
Unlike comparatively simple viruses and bacteria, malaria is a parasite with many stages to its life cycle and thousands of genes. That means it doesn’t always look the same to the immune system over time.
"That's a real technical challenge," says co-author Adrian Hill, vaccine expert and director of the Jenner Institute, to BBC News’ Philippa Roxby. "The vast majority of vaccines haven't worked because it's very difficult."
Both Mosquirix and R21 vaccines carry a single protein that the malaria parasite secretes during the first stage of its life cycle. That teaches the immune system to respond in full force if the person gets infected with malaria later.
R21 has a few key differences from previous vaccines. Compared to Mosquirix, it has more of the secreted protein per dose. The R21 vaccine is designed to be produced at a low cost so that it can be made widely available. The Serum Institute of India has already partnered with Oxford University to produce 200 million doses of the R21 vaccine if it is licensed.
“Definitely it’s exciting because of the possibility of large-scale production at relatively low cost,” says Nicholas White, a specialist in tropical medicine at Mahidol University who was not involved in the study, to Nature News. “But because it’s a small study, I don’t think you can say, ‘Wow, slam dunk, we’ve got a much better vaccine.’”
The R21 vaccine also targets the most dangerous form of the malaria parasite, but there are many varieties. Although the study gathered data for 12 months, the region where the study was conducted only faces a high risk of malaria for six months; in the latter half of the study, one child in the control group contracted malaria. Of 146 children who received the vaccine, 38 developed malaria, but the study did not include genetic analysis from those malaria cases.
As University of Florida malaria researcher Rhoel Dinglasan put it to Science magazine, “Where’s the biology?”
The Phase III trial will include regions that face malaria year-round, and continued study of the Phase II participants will illuminate whether the R21 vaccine holds its efficacy over time. Many other malaria vaccines are also in development, including some that try to introduce the immune system to more than a single protein at a time.
“I think R21 has now hit a ceiling for where we can go for this single-component vaccine,” says immunologist Stefan Kappe, an expert in malaria-parasite biology at the Seattle Children’s Research Institute, to Nature News. “From here on out, we need to build on additional components.”