BACKGROUND: Additional interventions are needed to reduce the morbidity and 
mortality caused by malaria.
METHODS: We conducted a two-part, phase 1 clinical trial to assess the safety 
and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an 
extended half-life, and its efficacy against infection with Plasmodium 
falciparum. Part A of the trial assessed the safety, initial side-effect 
profile, and pharmacokinetics of CIS43LS in healthy adults who had never had 
malaria. Participants received CIS43LS subcutaneously or intravenously at one of 
three escalating dose levels. A subgroup of participants from Part A continued 
to Part B, and some received a second CIS43LS infusion. Additional participants 
were enrolled in Part B and received CIS43LS intravenously. To assess the 
protective efficacy of CIS43LS, some participants underwent controlled human 
malaria infection in which they were exposed to mosquitoes carrying P. 
falciparum sporozoites 4 to 36 weeks after administration of CIS43LS.
RESULTS: A total of 25 participants received CIS43LS at a dose of 5 mg per 
kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 
25 participants received a second dose (20 mg per kilogram regardless of initial 
dose). No safety concerns were identified. We observed dose-dependent increases 
in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 
participants who received CIS43LS, as compared with 5 of 6 control participants 
who did not receive CIS43LS, had parasitemia according to 
polymerase-chain-reaction testing through 21 days after controlled human malaria 
infection. Two participants who received 40 mg per kilogram of CIS43LS and 
underwent controlled human malaria infection approximately 36 weeks later had no 
parasitemia, with serum concentrations of CIS43LS of 46 and 57 μg per milliliter 
at the time of controlled human malaria infection.
CONCLUSIONS: Among adults who had never had malaria infection or vaccination, 
administration of the long-acting monoclonal antibody CIS43LS prevented malaria 
after controlled infection. (Funded by the National Institute of Allergy and 
Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).