Low-dose monoclonal antibody injections prevent malaria infection
2023
Challenge
Malaria remains a major public health threat, with nearly half of the world’s population at risk of infection and children under five years old and pregnant women bearing the greatest burden of this disease. Although current interventions have contributed greatly to the considerable gains made against malaria since 2000, progress in developing effective, long-lasting vaccines has stalled and rates of malaria are increasing. Protection from the one malaria vaccine approved by the World Health Organization for use in malaria programs wanes over time and requires frequent boosting, as do several candidate vaccines in the research pipeline, As a result, creating high-level, lasting protection for communities against malaria remains a major challenge.
Advance
In a series of IRP-led clinical trials, researchers demonstrated that two monoclonal antibodies developed at NIH, CIS43LS and L9LS, provide high-level protection against all circulating malaria strains by targeting a section of malaria DNA that has been protected through natural selection. A single intravenous dose of CIS43LS was 88 percent protective against malaria infection in adults over a six-month period of intense malaria transmission in Mali. Additional clinical trials found that both CIS43LS and the L9LS protect against controlled malaria infection in U.S. adults. What’s more, these monoclonal antibodies were delivered at a low dose by subcutaneous injection under the skin, a simpler administration method. These advances could help make malaria prevention efforts more cost-effective and scalable, enabling potential global access to this important tool.
Impact
These initial trials provide hope that the two monoclonal antibodies developed by IRP researchers will be a powerful tool for preventing malaria symptoms and transmission between people in all age groups, improving health and economic well-being globally. Unlike vaccines that require multiple doses and take time to have an effect, monoclonal antibodies are immediately effective upon administration of a single dose. The length of time they remain effective is at least six months. Planned future clinical studies will explore their use for malaria prevention in key vulnerable populations, such as pregnant women and children, during specific periods of high malaria risk.
Publications
Lyke K, Berry A, Mason K, Idris AH, O'Callahan M, Happe M, Strom L, Berkowit z NM, Guech M, Hu Z, Castro M, Basappa M, Wang L, Low K, Holman LA, Mendoza F, Gordon IJ, Plummer SH, Trofymenko O, Strauss KS, Joshi S, Shrestha B, Adams M, Campos Chagas A, Murphy JR, Stein J, Hickman S, McDougal A, Lin B, Narpala SR, Vazquez S, Serebryannyy L, McDermott A, Gaudinski MR, Capparelli EV, Coates EE, Wu RL, Ledgerwood JE, Dropulic LK, Seder RA. (2023). Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody protects against malaria. Lancet Infect Dis. S1473-3099(22)00793-9. doi: 10.1016/S1473-3099(22)00793-9.
Kayentao K, Ongoiba A, Preston AC, Healy SA, Doumbo S, Doumtabe D, Traore A, Traore H, Djiguiba A, Li S, Peterson ME, Telscher S, Idris AH, Kisalu NK, Carlton K, Serebryannyy L, Narpala S, McDermott AB, Gaudinski M, Traore S, Cisse H, Keita M, Skinner J, Hu Z, Zéguimé A, Ouattara A, Doucoure M, Dolo A, Djimdé A, Traore B, Seder RA, and Crompton PD. (2022). Safety and efficacy of a monoclonal antibody against malaria in Mali. N Engl J Med. 387(20):1833-1842. doi: 10.1056/NEJMoa2206966.
Wu RL, Idris AH, Berkowitz NM, Happe M, Gaudinski MR, Buettner C, Strom C, Awan SF, Holman LA, Mendoza F, Gordon IJ, Hu Z, Campos Chagas A, Wang LT, Da Silva Pereira L, Francica JR, Kisalu NK, Flynn BJ, Shi W, Kong WP, O’Connell S, Plummer SH, Beck A, McDermott A, Narpala SR, Serebryannyy L, Castro M, Silva R, Imam M, Pittman I, Hickman SP, McDougal AJ, Lukoskie AE, Murphy JR, Gall JG, Carlton K, Morgan P, Seo E, Stein JA, Vazquez S, Telscher S, Capparelli EV, Coates EE, Mascola JR, Ledgerwood JE, Dropulic LK, Seder RA, (2022). Low-dose subcutaneous or intravenous monoclonal antibody to prevent malaria. N Engl J Med. 387(5):397-407. doi: 10.1056/NEJMoa2203067.
This page was last updated on Friday, November 24, 2023