Next-Generation Monoclonal Antibodies: Another Promising Approach to Malaria Prevention

In 2021, investigators showed that a monoclonal antibody could prevent Plasmodium falciparum malaria in adults challenged with malaria parasites (NEJM JW Infect Dis Oct 2021 and N Engl J Med 2021; 385:803). Now, researchers report results of a phase 1 trial of L9LS, a next-generation human IgG1 monoclonal antibody that is more potent and has a longer half-life. L9LS targets a highly conserved epitope on circumsporozoite protein-1 (CSP-1) in P. falciparum sporozoites. CSP-1 must be cleaved before sporozoites can invade hepatocytes; L9LS prevents this cleavage.

Of 27 enrolled adults with no history of malaria infection or vaccination, 18 received L9LS intravenously (1, 5, and 20 mg/kg) or subcutaneously (5 mg/kg). Controlled malaria infection …