Efficacy and safety of Monoclonal Antibodies in Malaria Protection and Prevention of Transmission: A Systematic Review.

PURPOSE: Despite advances in malaria control, progress toward elimination has stalled. Monoclonal antibodies (mAbs) have the capacity to provide rapid, long-lasting protection after a single administration. In this systematic review, we aimed to evaluate the efficacy, safety, and pharmacokinetic profiles of antimalarial mAbs-CIS43LS, L9LS, MAM01, and TB31F.

METHODS

We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for reporting this review. PubMed was searched from inception to 5 October 2025 for studies assessing the pharmacokinetics, safety, and efficacy of antimalarial mAbs. Eligible studies included Phases I and II clinical trials involving human participants.

FINDINGS: Seven studies (n = 776 participants) were included. CIS43LS and L9LS demonstrated dose-dependent protection against Plasmodium falciparum infection for up to 6 months. CIS43LS achieved protective efficacy of 75% to 88% at doses ≥10 mg/kg (intravenous), whereas L9LS showed efficacy of 66% to 77% following subcutaneous administration in Phase II trials. Both mAbs exhibited favorable safety profiles, with only grade 1 to 2 adverse events (local site reactions, headache, and fatigue) reported. Pharmacokinetic analyses revealed extended half-lives (CIS43LS: 56-80 days; L9LS: 46.1 days; MAM01: 71.1 days) supporting their potential for seasonal deployment. Phase I study of MAM01 demonstrated a favorable safety profile and dose-dependent pharmacokinetics. All participants in control group and 18 (of 22) participants in intervention arm developed parasitemia. One participant who had received 5 mg/kg (subcutaneous) and 3 who had received dose 40 mg/kg (intravenous) were protected and did not develop parasitemia. TB31F demonstrated transmission-reducing activity exceeding 80% at doses ≥1 mg/kg (intravenous and subcutaneous), sustained for up to 160 days after administration.

IMPLICATIONS: Antimalarial mAbs show promise as scalable tools for malaria prevention and transmission reduction. Subcutaneous delivery and prolonged protection enhance their feasibility for integration into the public health system for wider implementation in community settings. Further large-scale trials assessing long-term efficacy, operational feasibility, and cost-effectiveness in diverse settings, including children and pregnant women, are required and will govern the feasibility of its use in wider community settings.