An antibody drug called CIS43LS prevents malaria infection by interrupting the lifecycle of the Plasmodium falciparum parasite. The antibody binds to and neutralizes sporozoites, the stage of the parasite transmitted from mosquitos to humans. Credit: NIH
Key Points:
- One dose of a monoclonal antibody protected healthy adults in Africa during malaria season.
- The antibody was up to 88.2% effective at preventing infection over a 24-week period.
- Researchers hope to build on the success to bring treatment to vulnerable groups such as infants, children, and pregnant women.
An NIH-developed monoclonal antibody was up to 88.2% effective at preventing infection in healthy, non-pregnant adults during an intense 6-month malaria season in Mali, Africa. This is the first time a monoclonal antibody has been shown to prevent malaria infection in an endemic region.
The monoclonal antibody, called CIS43LS, was previously shown to neutralize the sporozoites of P. falciparum in the skin and blood before they could infect liver cells. Researchers led by Robert A. Seder, M.D., isolated a naturally occurring form of the antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to extend the length of time it would remain in the bloodstream.
The Phase 2 trial evaluated the safety and efficacy of a one-time, intravenous infusion of CIS43LS in 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where intense P. falciparum transmission typically occurs from July through December each year.
The first part of the trial assessed the safety of three different doses of CIS43LS—all of which were found to be safe and well-tolerated. The second part of the trial assessed the efficacy of two different doses of CIS43LS compared with a placebo. At random, 330 participants were assigned to receive either 10 mg/kg of the antibody, 40 mg/kg, or a placebo by intravenous infusion. The study team followed these individuals for 24 weeks, testing their blood for P. falciparum weekly for the first 28 days and every two weeks thereafter.
Researchers analyzed the efficacy of CIS43LS in two ways. Based on the time to first P. falciparum infection over the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective at preventing infection and the lower dose (10 mg/kg) was 75% effective. An analysis of the proportion of participants infected with P. falciparum at any time over the 24-week study period found the high dose was 76.7% at preventing infection and the lower dose was 54.2% effective.
“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 Seder. “We hope monoclonal antibodies will transform malaria prevention in endemic regions.”
The only malaria vaccine currently recommended by WHO, called RTS,S (Mosquirix), provides partial protection against clinical malaria during the early years of life when given to children aged 5 to 17 months in four doses over a 20-month period.
Information provided by NIH.