Using monoclonal antibodies to prevent malaria



Malaria is a serious health threat across the world, and some groups and regions, such as children in sub-Saharan Africa, are particularly vulnerable. While a first-of-its-kind malaria vaccine was recently approved in Africa for use in infants ages 5 to 17 months old, it is only 36 percent effective at preventing the illness after four years. Thus, there is a critical need for new interventions that are highly effective at providing sustained protection from malaria in infants, young children, and pregnant women.


IRP investigators led by Robert Seder, M.D., isolated a monoclonal antibody, CIS43, from an individual who received an investigational malaria vaccine. In animal studies, the researchers found that CIS43 prevents infection by binding to the surface of a protein on the parasite responsible for malaria, Plasmodium falciparum. The research team then introduced a change into the CIS43 antibody that lengthened the amount of time it remains active in the body, producing a new version they named CIS43LS. In a first-in-human Phase 1 clinical trial, the CIS43LS antibody was found to be safe when administered to healthy adults. In addition, when participants were exposed to mosquitoes infected with Plasmodium parasites 4-36 weeks after receiving CIS43LS, all of the participants who received CIS43LS were protected from malaria infection.


This study provides the first evidence that administration of an anti-malaria antibody is safe and can prevent malaria infection in humans. The ability of an antibody to provide high-level protection for 6-12 months following a single administration may lead to immediate control of malaria in infants, young children, and pregnant women, potentially saving hundreds of thousands of lives. Moreover, a monoclonal antibody-based vaccine provides a potential tool to eliminate malaria, which would vastly improve health and economic well-being around the world.


Gaudinski MR, Berkowitz NM, Idris AH, Coates EE, Holman LA, Mendoza F, Gordon IJ, Plummer SH, Trofymenko O, Hu Z, Campos Chagas A, O'Connell S, Basappa M, Douek N, Narpala SR, Barry CR, Widge AT, Hicks R, Awan SF, Wu RL, Hickman S, Wycuff D, Stein JA, Case C, Evans BP, Carlton K, Gall JG, Vazquez S, Flach B, Chen GL, Francica JR, Flynn BJ, Kisalu NK, Capparelli EV, McDermott A, Mascola JR, Ledgerwood JE, Seder RA; VRC 612 Study Team. (2021). A monoclonal antibody for malaria prevention. N Engl J Med. Aug 26;385(9):803-814. doi: 10.1056/NEJMoa2034031.

Kisalu NK, Idris AH, Weidle C, Flores-Garcia Y, Flynn BJ, Sack BK, Murphy S, Schön A, Freire E, Francica JR, Miller AB, Gregory J, March S, Liao HX, Haynes BF, Wiehe K, Trama AM, Saunders KO, Gladden MA, Monroe A, Bonsignori M, Kanekiyo M, Wheatley AK, McDermott AB, Farney SK, Chuang GY, Zhang B, Kc N, Chakravarty S, Kwong PD, Sinnis P, Bhatia SN, Kappe SHI, Sim BKL, Hoffman SL, Zavala F, Pancera M, Seder RA. (2018). A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med. May;24(4):408-416. doi: 10.1038/nm.4512.

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This page was last updated on Thursday, June 8, 2023