• Martin R Gaudinski, Nina M Berkowitz, Azza H Idris, Emily E Coates, LaSonji A Holman, Floreliz Mendoza, Ingelise J Gordon, Sarah H Plummer, Olga Trofymenko, Zonghui Hu, Andrezza Campos Chagas, Sarah O'Connell, Manjula Basappa, Naomi Douek, Sandeep R Narpala, Christopher R Barry, Alicia T Widge, Renunda Hicks, Seemal F Awan, Richard L Wu, Somia Hickman, Diane Wycuff, Judy A Stein, Christopher Case, Brian P Evans, Kevin Carlton, Jason G Gall, Sandra Vazquez, Britta Flach, Grace L Chen, Joseph R Francica, Barbara J Flynn, Neville K Kisalu, Edmund V Capparelli, Adrian McDermott, John R Mascola, Julie E Ledgerwood, Robert A Seder, and VRC 612 Study Team.
• From the Vaccine Research Center (M.R.G., N.M.B., A.H.I., E.E.C., L.A.H., F.M., I.J.G., S.H.P., O.T., S.O., M.B., N.D., S.R.N., C.R.B., A.T.W., R.H., S.F.A., R.L.W., S.H., D.W., J.A.S., K.C., J.G.G., S.V., B.F., G.L.C., J.R.F., B.J.F., N.K.K., A.M., J.R.M., J.E.L., R.A.S.) and the Biostatistics Research Branch, Division of Clinical Research (Z.H.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, the U.S. Public Health Service Commissioned Corps, Rockville (M.R.G.), the Entomology Branch, Walter Reed Army Institute of Research, Silver Spring (A.C.C., B.P.E.), and the Vaccine Clinical Materials Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick (C.C.) - all in Maryland; and the School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego (E.V.C.).
• N. Engl. J. Med. 2021 Aug 26; 385 (9): 803814803-814.

BackgroundAdditional interventions are needed to reduce the morbidity and mortality caused by malaria.MethodsWe 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.ResultsA 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.ConclusionsAmong 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.).Copyright © 2021 Massachusetts Medical Society.

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