A Monoclonal Antibody for Malaria Prevention
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
Abstract
BACKGROUND: Additional interventions are needed to reduce the morbidity and mortality caused by malaria. METHODS: 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.).