A single dose of a drug protected healthy adults and non-pregnant women from malaria infection during an intense six-month malaria season in Mali, Africa, according to a US National Institutes of Health clinical trial. The monoclonal antibody achieved up to 88.2% efficacy in preventing infection over a 24-week period, demonstrating for the first time that a monoclonal antibody can prevent malaria infection in an endemic region.
These results have been published in “The New England Journal of Medicine”.
“We need to expand the arsenal of interventions available to prevent malaria infection and accelerate efforts to eliminate the disease,” says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID). “The results of this study suggest that a monoclonal antibody could potentially complement other measures to protect travelers and vulnerable groups, such as infants, children and pregnant women, from seasonal malaria and help eliminate malaria from geographical areas.” defined”.
According to the World Health Organization (WHO), an estimated 241 million cases of malaria occurred worldwide in 2020, causing some 627,000 deaths, mostly in children in sub-Saharan Africa. Among these cases are more than 11 million pregnant women in Africa, which will result in some 819,000 newborns with low birth weight and, therefore, with increased risk of disease and death.
The only malaria vaccine currently recommended by WHO, called RTS (Mosquirix), provides partial protection against clinical malaria during the first years of life when given to children aged 5 to 17 months in four doses over a period of 20 months. There are also other drugs made up of small chemical compounds that effectively prevent malaria infection for infants and young children, as well as for travellers.
However, the need for frequent dosing of these drugs may limit adherence, and the development of drug resistance may also limit their usefulness. Therefore, there is an urgent need for new rapid-acting, infrequent-dose interventions that safely provide strong protection against malaria infection.
Malaria is caused by Plasmodium parasites, which are transmitted to people through the bite of an infected mosquito. The mosquito injects the parasites in a form called sporozoites into the skin and bloodstream. These travel to the liver, where they mature and multiply. The mature parasite then spreads throughout the body through the bloodstream to cause disease. P. falciparum is a species of Plasmodium more likely to cause serious malaria infections which, if not treated promptly, can lead to death.
This trial evaluated the safety and efficacy of a single intravenous infusion of a monoclonal antibody called CIS43LS. This antibody had previously been shown to neutralize P. falciparum sporozoites in skin and blood before they could infect liver cells.
The researchers, led by Robert A. Seder of the Vaccine Research Center (VRC), isolated a natural form of this antibody from the blood of a volunteer who had received an investigational malaria vaccine, and then modified the antibody to prolong its stay in the bloodstream.
There is an urgent need for new rapid-acting malaria interventions
The phase 2 study team recruited 369 healthy, non-pregnant adults aged 18 to 55 years in the rural communities of Kalifabougou and Torodo in Mali, where P. falciparum transmission is typically intense from July to December of each year.
The second part of the trial evaluated the efficacy of two different doses of CIS43LS compared to placebo. Three hundred and thirty participants were randomly assigned to receive 10 mg/kg of the antibody, 40 mg/kg, or placebo by intravenous infusion. No one knew who had been assigned to which group until the end of the trial.
The team followed these people for 24 weeks, testing their blood for P. falciparum weekly for the first 28 days and every two weeks thereafter. Any participant who developed symptomatic malaria during the trial received standard treatment from the study team.
These results pave the way for further studies to determine whether such an intervention can prevent malaria infection in infants, children and pregnant women.
Robert A. Seder
Vaccine Research Center
The researchers tested the efficacy of CIS43LS in two ways. Based on the time to first P. falciparum infection during the 24-week study period, the high dose (40 mg/kg) of CIS43LS was 88.2% effective in preventing infection, and the high dose The lowest (10 mg/kg) had an efficacy of 75%. An analysis of the proportion of participants infected with P. falciparum at any time during the 24-week study period revealed that the high dose was 76.7% effective in preventing infection and the lower dose 54.2%.
“These early results pave the way for further studies to determine whether such an intervention can prevent malaria infection in infants, children, and pregnant women,” says Seder. «We hope monoclonal antibodies will transform malaria prevention in endemic regions».
Seder and colleagues have developed a second antimalarial monoclonal antibody, L9LS, which is much more potent than CIS43LS and therefore can be given in a smaller dose as an injection under the skin (subcutaneously), rather than by intravenous infusion .
An early-stage US trial found that the antibody was safe and prevented malaria infection for 21 days in 15 of 17 healthy adults exposed to P. falciparum in a carefully controlled setting.
Two larger phase 2 trials are underway in Mali and Kenya to assess the safety and efficacy of L9LS in infants, children and adults.