A novel monoclonal antibody, CIS43LS, has shown promising results in preventing malaria in a Phase 1 clinical trial. The study, conducted by researchers at the National Institutes of Health (NIH), demonstrated that a single dose of the antibody provided protection against malaria for up to nine months in individuals exposed to the malaria parasite, Plasmodium falciparum. This marks the first time a monoclonal antibody has been shown to prevent malaria in humans.
The research, published in the New England Journal of Medicine, highlights the potential of CIS43LS as a preventative measure against malaria, a disease that remains a major global health challenge. Current malaria vaccines offer limited protection, with none exceeding 50% efficacy over a year or longer after Phase 3 testing.
Mechanism of Action
CIS43LS is a modified version of a naturally occurring neutralizing antibody, CIS43, which was discovered by Dr. Robert Seder and his team at the Vaccine Research Center (VRC) at NIAID. CIS43 binds to a unique site on a parasite surface protein present on all variants of P. falciparum sporozoites worldwide, effectively neutralizing the parasite before it can infect liver cells.
Clinical Trial Results
The Phase 1 clinical trial involved two stages. In the first stage, participants received a single dose of CIS43LS. In the second stage, participants volunteered to undergo controlled human malaria infection (CHMI), where they were exposed to P. falciparum through the bites of infected mosquitoes under carefully controlled conditions. Nine participants who had received CIS43LS underwent CHMI and were monitored for 21 days. None of them developed malaria, while 5 out of 6 control participants did. Further analysis indicated that a single dose of the experimental antibody could prevent malaria for 1 to 9 months after infusion.
Future Directions
Building on these findings, a larger NIAID-sponsored Phase 2 clinical trial is currently underway in Mali during a 6-month malaria season to assess the efficacy and safety of CIS43LS in a real-world setting. According to Dr. Seder, monoclonal antibodies like CIS43LS could offer a new approach to preventing malaria in travelers, military personnel, and healthcare workers traveling to malaria-endemic regions. Further research will explore the potential of monoclonal antibodies for malaria-elimination campaigns.
