Malaria prevention is expected to 'upgrade'

Injection of antibodies against plasmodium falciparum sporophyte stage proteins protects the person from malaria. Image credit: DENNIS KUNKEL MICROSCOPY

In a recent study, nine people who received monoclonal antibodies were deliberately exposed to mosquitoes carrying the malaria parasite. The results showed that no one was infected, and this protective effect seemed to last for more than half a year.

"This is a landmark study." Dennis Burton, an immunologist at the Scripps Institute in the United States, said. Trials have opened up a new avenue for preventing this deadly disease.

Despite the high cost of producing monoclonal antibodies, this work informs the development of a better vaccine than the malaria vaccine currently in widespread use. It shows the importance of targeting the immune response at key regions of protein produced in the sporophyte stage of Plasmodium falciparum. Plasmodium falciparum is the protozoa responsible for most malaria deaths in the world, causing at least 200 million people to become ill each year and about 400,000 deaths. Plasmodium falciparum has a complex, multi-stage life cycle and is resistant to antimalarial drugs.

This prophylactic antibody binds to a small subset of cyclosporid proteins (CSPs), which are located on the surface of these sporozoites. "This is the first time that the efficacy of antibodies against CSP targets in humans has been actually evaluated." Hedda Wardemann, an immunologist at the German Cancer Research Center, said.

For the first time, the team isolated the CSP antibody from a person who received a trial malaria vaccine. Previous studies analyzed the genetic makeup of 6500 Plasmodium falciparum isolates and found that 99.9% of the isolates were identical in the target region of this antibody. The "highly conserved" nature of the CSP region means that the parasite needs it to survive, so the researchers reasoned that it cannot easily mutate in a way that avoids antibodies.

The team, led by Robert Seder, an immunologist at the National Center for Allergy and Infectious Disease Vaccine Research, genetically engineered a large number of modified antibodies to more than double the time it survives in vivo before degradation. The team injected the subjects with this antibody and then had mosquitoes carrying Plasmodium falciparum bite the subjects' arms. A few days ago, the research team reported in the New England Journal of Medicine that in this "challenge" trial, the researchers did not detect parasites in the blood of people who were injected with antibodies, while in the control group, 5 out of 6 people detected parasites in blood.

Ideally, Seder said, a relatively low dose of antibody should be delivered by subcutaneous injection, which is easier and cheaper than blood injections in the study to provide relatively high doses of antibodies.

In addition, in 2019, 3 African countries began large-scale testing of a pilot malaria vaccine called RTS,S, which targets different parts of the CSP. As of April, the pilot project had given 650,000 children four doses of the vaccine. In early clinical trials, the vaccine reduced the infection rate in children by 50% after 1 year, and by year 4, that number dropped to 28%. Wardemann said it is hoped that larger studies will be conducted on the monoclonal vaccine developed by Seder et al. to determine which parts of CSP can stimulate a more effective or long-lasting immune response. (Bunraku)

Related thesis information: https://doi.org/10.1056/NEJMoa2034031

Source: China Science Daily