Monoclonal Antibody Prevents Malaria in U.S. Adults

One injection of a candidate monoclonal antibody (mAb) known as L9LS was found to be safe and highly protective in U.S. adults exposed to the malaria parasite, according to results from a NIAID phase 1 clinical trial published in the New England Journal of Medicine. 

Additional clinical trials evaluating whether L9LS can prevent malaria over 6 to 12 months against seasonal and perennial transmission are underway in infants and children in Mali and Kenya, where malaria is endemic. 

Malaria is a mosquito-borne disease caused by Plasmodium parasites. The World Health Organization estimates that in 2020 about 240 million people had malaria and about 627,000 died, many of them young children. 

A vaccine to prevent malaria is now available; however, its variable efficacy underscores the need for new interventions that protect against disease.

Scientists from NIH’s Vaccine Research Center developed L9LS and led the phase 1 clinical trial. L9LS is a laboratory-made version of a naturally occurring antibody called L9, derived from the blood of a volunteer who had received an investigational malaria vaccine. The antibody prevents malaria by neutralizing the parasites in the skin and blood before they can infect liver cells.

The study was conducted from Sept. 13 to Nov. 16, 2021, at the Clinical Center and the Walter Reed Army Institute of Research in Silver Spring, Md. The trial involved 18 volunteers receiving various doses of L9LS subcutaneously or intravenously. 

After tolerating the injection and experiencing no safety concerns, participants allowed mosquitoes carrying the malaria parasite to bite their forearm 5 times, starting from 2 to 6 weeks after receiving the mAb candidate. 

This took place in a carefully controlled setting, known as controlled human malaria infection (CHMI). As part of this approach, which has been used for decades in malaria research, medical staffers closely monitor participants and provide proper treatment if they become infected. 

L9LS fully protected 15 of 17 (88 percent) participants from malaria infection during the 21-day challenge period. All volunteers in the control group that underwent CHMI, but did not receive L9LS, became infected and were promptly treated without complications. Encouragingly, 4 of the 5 participants who received a low, subcutaneous dose of the mAb were protected from malaria. 

NIAID director Dr. Anthony Fauci said the results are promising: “A one-time intervention that protects against malaria for 6 months to a year could significantly reduce morbidity and mortality among children in malaria-endemic regions and offer an effective preventive tool for health care workers, military personnel and travelers to these areas.”