A National Institutes of Health (NIH) clinical trial has revealed that a single dose of the monoclonal antibody CIS43LS can safely and effectively prevent malaria infection in healthy, non-pregnant adults during a six-month malaria season in Mali, Africa. The study, published in The New England Journal of Medicine, found the antibody to be up to 88.2% effective over a 24-week period, marking a significant milestone as the first demonstration of a monoclonal antibody preventing malaria infection in an endemic area.
Efficacy of CIS43LS in Malaria Prevention
The Phase 2 trial, sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), involved 369 adults aged 18-55 years in rural Mali. Participants received a single intravenous infusion of either CIS43LS (at doses of 10 mg/kg or 40 mg/kg) or a placebo. The high dose (40 mg/kg) of CIS43LS demonstrated 88.2% efficacy in preventing P. falciparum infection, while the lower dose (10 mg/kg) showed 75% efficacy, based on the time to first infection over the 24-week study period.
An alternative analysis, assessing the proportion of participants infected at any point during the study, revealed that the high dose of CIS43LS was 76.7% effective, and the lower dose was 54.2% effective.
The Need for New Malaria Interventions
Malaria remains a significant global health challenge, with an estimated 241 million cases and 627,000 deaths reported worldwide in 2020, according to the World Health Organization (WHO). Sub-Saharan Africa bears the brunt of the disease, particularly affecting children and pregnant women. Current interventions, such as the RTS,S vaccine and prophylactic drugs, face limitations including partial protection, adherence challenges due to frequent dosing, and the emergence of drug resistance.
Mechanism of Action and Antibody Development
CIS43LS works by neutralizing Plasmodium falciparum sporozoites in the skin and blood, preventing them from infecting liver cells. The antibody is a modified version of a naturally occurring antibody isolated from a volunteer who received an investigational malaria vaccine. The modification extends the antibody's duration in the bloodstream, providing prolonged protection.
Future Directions and Alternative Antibodies
Building on the success of CIS43LS, researchers have developed a more potent antimalarial monoclonal antibody called L9LS. Early-phase trials in the United States have shown that L9LS, administered subcutaneously, is safe and effective in preventing malaria infection. Two larger Phase 2 trials are currently underway in Mali and Kenya to assess the safety and efficacy of L9LS in infants, children, and adults.
"These first field results demonstrating that a monoclonal antibody safely provides high-level protection against intense malaria transmission in healthy adults pave the way for further studies to determine if such an intervention can prevent malaria infection in infants, children, and pregnant women," said Dr. Seder.
Trial Information
Additional information about the Phase 2 trial of CIS43LS is available at ClinicalTrials.gov under study identifier NCT04329104.
