An experimental malaria vaccine showed protection against artificially induced malaria infection in a randomized, double-blind Phase 2 trial in Sotuba, a district near Bamako in Mali. Vaccinated adults developed parasite-confirmed malaria less frequently than a control group. Depending on calculation method, efficacy reached 76 or 54 percent, according to The Lancet Infectious Diseases report on candidate ProC6C-AlOH/Matrix-M published in December 2025.
Thirty-four participants, 15 men and 19 women, received vaccinations on March 20, April 15, and May 9, 2024. Healthy, malaria-experienced adults aged 18 to 50 were randomly assigned in a 1:1 ratio to receive three vaccinations four weeks apart: either the candidate containing 100 micrograms of ProC6C and 50 micrograms of Matrix-M, or the rabies vaccine Verorab as control.
By day 28 after infection, 19 of 32 participants, or 59 percent, developed detectable parasites in blood: 13 of 16 in the control group versus six of 16 in the vaccine group. Using time-to-event analysis in the per-protocol population, this yielded 76 percent efficacy with a 95 percent confidence interval of 36 to 91 percent. A second calculation using risk ratio showed 54 percent efficacy with a wider confidence interval of 9 to 77 percent. Among vaccinated participants who developed infection, parasite detection in blood was delayed by a median of two days, from 12 to 14 days.
Adverse events in vaccine group mostly mild
The vaccine was well tolerated. At least one adverse event occurred in 13 of 17 vaccine recipients compared to three of 17 in the control group, with almost all vaccine group events being mild.
How researchers interpret the results
Study authors describe this as the first clinical trial of an anti-PfCSP subunit vaccine achieving over 50 percent efficacy against controlled infection 12 weeks after final dose, describing a novel, mechanistically plausible protection correlate. Statens Serum Institut, involved in development, stated the vaccine should combine protection against infection with reduced transmission to mosquitoes. According to the institute, the candidate also reduced mosquito transmission. Involved researcher Michael Theisen noted this study type, combining human and mosquito components, was used for the first time with a multistage vaccine, but called for confirmation in larger studies.
Earlier findings on the vaccine
A single dose of ProC6C-AlOH/Matrix-M induced seroconversion against target protein PfCSP in 19 of 20 volunteers. Thirteen of 20 volunteers in this group (65 percent) also showed transmission-reducing activity greater than 80 percent, correlating with antibody levels against protein Pfs48/45. The current Mali trial groups of 17 vaccinated per arm are smaller than the 20-person groups from earlier studies.
Experience with controlled infection trials
The eight participants rated their participation as positive overall, though some expressed concerns about frequent blood draws or study schedules conflicting with university commitments. Study authors emphasize that deliberately infecting healthy volunteers contradicts the principle of first doing no harm, and call for careful ethical review, as financial compensation could incentivize participation among people with limited income.
Further research on efficacy in children
Study authors recommend investigating efficacy against naturally acquired clinical malaria and transmission in preschool and school-age children after gradual age-group inclusion in future Phase 2 trials with ProC6C. The institute also announced further studies, including possible field investigations in children, who they note are particularly vulnerable to malaria and contribute most to transmission. Theisen emphasized the results must be confirmed in larger trials. If individual protection combines with reduced transmission, such a vaccine could prove significant for malaria control in heavily affected regions.