One dose of a new monoclonal antibody discovered and developed at the National Institutes of Health might be all it takes to protect people from malaria for nearly a year, according to researchers behind a new study published in the New England Journal of Medicine.
Malaria is a preventable mosquito-borne disease that can result in fever, headaches, seizures and, in serious cases, coma or death.
“This is a landmark study,” said Dennis Burton, an immunologist at Scripps Research who developed monoclonal antibodies to prevent HIV infection, COVID-19 and Zika, according to ScienceMag.
Monoclonal antibodies are copies of antibodies, which are proteins that fight foreign bacteria and viruses. Monoclonal antibodies have been approved or authorized for emergency use for inflammatory diseases, cancer and viral infections.
NIH’s early-stage study enrolled 40 healthy adults and tested whether a monoclonal antibody, called CIS43LS, could provide a high level of protection from malaria. The study looked at the effects of controlled exposure to mosquitoes carrying a parasite called Plasmodium falciparum, the protozoan responsible for most of the world’s malaria deaths. The parasite kills over an estimated 409,000 people — 67% of whom are under 5 years old — and sickens at least 200,000 more per year, according to the World Health Organization.
Fifteen of the volunteers were exposed to bites from the mosquitoes. Shockingly, none of the nine participants who received CIS43LS developed malaria, compared with five of the six who did not receive the drug. This protection is also estimated to last for up to over six months, with one participant having protection for nine months.
Because the trial involved just 40 people, it is too small for researchers to reach concrete conclusions about the efficacy of the monoclonal antibodies. However, many in the field are impressed by the study, which provides key findings for preventing the deadly disease.
“Monoclonal antibodies may represent a new approach for preventing malaria in travelers, military personnel and health care workers traveling to malaria-endemic regions,” said Robert Seder, study coauthor and chief of the Cellular Immunology Section of NIH’s Vaccine Research Center Immunology Laboratory. “Further research will determine whether monoclonal antibodies can also be used for the seasonal control of malaria in Africa and ultimately for malaria-elimination campaigns.”
Vaccine research has been quite successful recently — preliminary results suggest that one vaccine is up to 77% effective in young children. However, the only licensed malaria vaccine, Mosquirix, is around 30% effective. This research could further efforts to develop a malaria vaccine more effective than the one widely used now.
There are already drugs that can temporarily protect people from contracting the disease, and insecticides and bed nets help lower the transmission rate, but the rate of infection is still very high.
P. falciparum is notable for having high resistance to antimalarial drugs, which is why malaria prevention has been so difficult. However, the specific region that the monoclonal antibodies target is “highly conserved” according to researchers, meaning that the parasite needs that region to survive and therefore won’t mutate in a way that avoids the antibody. This means that the antibody may remain effective for quite awhile.
Preventing malaria for several months with one dose of CIS43LS could be valuable in regions where malaria cases increase during rainy seasons. Monoclonal antibodies do have rather high production costs, but the antibodies can be manufactured in bulk. Because children have not had much time to develop natural immunity, the antibodies will be helpful for younger populations most affected by malaria.
Seder is developing a new monoclonal antibody that’s two to three times as potent. Results of a larger, mid-stage trial to assess CIS43LS during malaria season in Mali are expected to come out next year.
“Monoclonal antibodies may represent a new approach for preventing malaria in travelers, military personnel and health care workers traveling to malaria-endemic regions,” said Seder. “Further research will determine whether monoclonal antibodies can also be used for the seasonal control of malaria in Africa and ultimately for malaria-elimination campaigns.”
