THURSDAY, August 4, 2022 (HealthDay News) — Researchers report early but encouraging results on a potential new way to prevent malaria — an old foe still considered the world’s top killer.
In a small study of healthy volunteers, US government researchers found that a lab-made antibody protected most participants from infection with the malaria parasite, including those receiving higher doses of the antibody.
The researchers also showed that it was possible to administer the antibody using a standard injection, rather than the IV infusions typically used to administer monoclonal antibodies. That will be crucial, the researchers said, for use in the “real world.”
Experts warn that there is still a lot of work to be done. But they also described the findings as an “exciting” development against a major child killer in developing countries.
Malaria is caused by a parasite carried by certain species of mosquitoes. Despite various prevention efforts – from insecticide-treated bed nets to disease-preventing drugs – malaria continues to take a huge toll.
In 2020, more than 240 million people contracted malaria and over 600,000 died – mostly children under the age of 5 in sub-Saharan Africa.
“Imagine being a parent living in a place with high malaria transmission,” said Dr. Robert Seder from the US National Institute of Allergy and Infectious Diseases. “Your child could die from a mosquito bite.”
Last year saw a major step in the fight against the disease when the World Health Organization approved the first-ever malaria vaccine for use in young children. The vaccine, called Mosquirix, is given in three doses between ages 5 and 17 months, with a fourth dose about 18 months later.
Although the vaccine has been hailed as a breakthrough, it is not a home run. On average, it reduces a child’s risk of malaria by about 36% over the age of four.
“We want to improve that,” said Seder, the lead researcher on the new study.
Developing a highly effective vaccine against malaria is difficult because of the complexity of the parasitic infection, Seder explained.
The malaria pathogen goes through different stages of life in the human body. When an infected mosquito bites someone, it “spits out” a small number of parasites in a form called sporozoites into the blood. These sporozoites then migrate to the liver, where they multiply and mature.
Eventually, the parasites make their way into the blood cells, where they cause illness — typically fever and other flu-like symptoms. Without prompt treatment, it can lead to serious complications such as organ failure and brain swelling.
Seder and his colleagues have developed a different approach to prevention: a monoclonal antibody that recognizes a protein on the surface of the sporozoite to stop it from entering the liver. The antibody is a laboratory-modified version of a natural antibody isolated from a patient who had been vaccinated against malaria.
In theory, a monoclonal antibody could work better than a vaccine, Seder said: Vaccines rely on training the immune system to produce antibodies against a foreign invader, and that response will vary from person to person.
Monoclonal antibodies are more predictable.
“They are administered at a protective dose, like filling a gas tank,” said Dr. Johanna Daily, an infectious disease specialist at the Albert Einstein College of Medicine in New York City.
Daily, which studies malaria, wrote an editorial published August 4 with the new findings in New England Journal of Medicine.
“I’m excited about that,” Daily said of the antibody approach.
Monoclonal antibodies are “very specific” to the invader they are targeting, she said, and if that can be delivered through a standard jab, it would be possible for use in the countries where it is most needed.
The current study involved 23 healthy US adults, 17 of whom received the monoclonal antibody either intravenously or by injection. The remaining six served as a comparison group. All were exposed voluntarily and under controlled conditions to mosquitoes carrying the malaria parasite.
Of the 17 who received the antibody, 15 were fully protected and had no detectable parasite in their blood three weeks after controlled infection. That included all of the volunteers who were given a higher dose of the antibody.
In contrast, all six people in the comparison group had parasites in their blood (and were being treated with standard antimalarial drugs).
The antibody used by Seder’s team is a more potent form of an antibody they tested in a previous study published a year ago. Researchers estimate that this new version could protect a young child from malaria for 6 to 12 months after one injection.
“We’ve shown that you can give it the standard route, rather than IV, and you don’t have to give very much – which leads to the cost issue,” Seder noted.
The downside of monoclonal antibodies is that they eventually deplete and injections would have to be repeated to get children through the high-risk years.
One benefit, Seder said, is that any antibodies engineered are highly targeted to the parasite — in contrast to the differential response a vaccine elicits, where some antibodies are very effective and others not so much.
“It’s like having a team where everyone is Michael Jordan,” Seder said.
A real-world study of the approach is already underway in Mali, and another is set to begin in Kenya, Seder noted.
If the tactic proves effective, Daily said, one question will be how to integrate it with existing prevention efforts, including the vaccine. One way, Seder said, could be to vaccinate babies and then give the antibody as a booster shot — maybe annually, for several years.
A bigger question, for both the vaccine and the antibody, is whether the parasite will evolve to evade them. Only time will tell, Daily said.
The US National Institute of Allergy and Infectious Diseases has more on malaria.
SOURCES: Robert Seder, MD, Vaccine Research Center, US National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Johanna Daily, MD, MS, Professor of Medicine, Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY; New England Journal of Medicine, August 4, 2022
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