Malaria is a mosquito-borne disease caused by the parasite Plasmodium. The World Health Organization estimates that by 2020, about 240 million people will contract malaria and about 627,000 of them will have died. A disproportionate burden of malaria is seen in sub-Saharan Africa, where children under the age of 5 account for about 80% of all malaria deaths. A vaccine for malaria is now available; However, its varying efficacy highlights the need for novel interventions that provide high levels of protection against disease.
Scientists from NIH’s Vaccine Research Center (VRC), part of NIAID, developed L9LS and led the Phase 1 clinical trial. L9LS is a lab-created version of L9LS. a natural antibody called L9, derived from the blood of a volunteer who received the investigational malaria vaccine. This antibody prevents malaria by neutralizing the parasites in the skin and blood before they can infect liver cells.
L9LS is similar to a candidate antimalarial antibody called CIS43LS that VRC has developed and found to be highly protective in a small trial when administered intravenously. However, the L9LS is two to three times more powerful. Increased potency allows for subcutaneous injection, a more feasible and effective route than intravenous infusion.
The Phase 1 study was conducted from September 13 to November 16, 2021, at the NIH Clinical Center in Bethesda, Maryland and the Walter Reed Army Research Institute (WRAIR) in Silver Spring, Maryland. The trial involved 18 volunteer participants who received different doses of L9LS by subcutaneous or intravenous injection. After accepting the injection and not having any safety concerns, the participants allowed the malaria-carrying mosquito to bite their forearm five times, starting two to six weeks after receiving the application. mAb candidate.
This takes place in a carefully controlled environment, known as controlled human malaria infection (CHMI). As part of this approach, which has been used for decades in malaria research, health workers closely monitor participants and give appropriate treatment if they become infected. . L9LS completely protected 15 of 17 (88%) participants from malaria infection during the 21-day challenge period. All volunteers in the control group who underwent CHMI, but did not receive L9LS, developed infections and were promptly treated without complications. It is encouraging that four out of five participants who received a low dose of mAb subcutaneously were protected from malaria.
Robert Seder, MD, Head of Cellular Immunology, said: “This is the first demonstration that a monoclonal antibody can be protective when administered subcutaneously, which has important implications for its use. widely used in clinical practice and achieve the goal of malaria elimination. VRC, who led the development of the L9LS. “We expect results in larger field studies to help establish effective dosing.”