Results from a Phase I clinical trial have shown that a monoclonal antibody known as L9LS is safe and highly protective in U.S. adults exposed to the malaria parasite. The use of this antibody could be effective in limiting malaria in regions of the world where the disease is endemic. According to the World Health Organization, about 240 million people had malaria in 2020 and about 627,000 of them died.
“These early clinical trial results demonstrating that a monoclonal antibody administered subcutaneously can protect people from malaria are highly encouraging,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), which sponsored the trial.
Scientists from the Vaccine Research Center (VRC), part of the NIAID at the National Institutes of Health (NIH), developed L9LS and led the Phase I clinical trial. They published their findings in The New England Journal of Medicine (“Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria”).
A vaccine for malaria is available but its efficacy is variable. “Monoclonal antibodies are a promising solution to the problem of overcoming host and parasite factors that can present challenges to the generation of highly protective and durable vaccine-induced immunity to malaria,” the scientists wrote. “A durable and potent monoclonal antibody delivered subcutaneously to infants and children could be an effective intervention to limit malaria-related morbidity and mortality worldwide over prolonged periods.”
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.
In the trial, 17 participants received an injection of L9LS at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight. These participants, along with six control participants, were exposed to mosquitoes carrying the malaria-causing parasite Plasmodium within 2 to 6 weeks after the administration of L9LS.
Of the 17 L9L2 participants, 15 (88%) were protected. All six control participants developed malaria infection, as did two of the L9L2 participants. The antibody had an estimated half-life of 56 days, and no safety concerns were identified.
“These findings may have important public health and clinical implications because they establish the potential to advance protection against malaria in regions with seasonal and perennial transmission,” the researchers wrote. Phase II clinical trials are underway to evaluate whether L9LS can prevent malaria in infants and children in Mali and Kenya, where malaria is endemic.
“We look forward to results in larger field studies that will help establish an effective dose,” said Robert Seder, MD, who led the development of L9LS.
Richard Wu, MD, staff clinician in the VRC’s Clinical Trials Program, led the Phase I trial. Study collaborators included scientists from the U.S. Public Health Service Commissioned Corps; the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University; NIAID’S Biostatistics Research Branch; WRAIR; and the University of California at San Diego.