The promise of monoclonal antibody interventions in malaria: a narrative review

Malaria remains a leading cause of morbidity and mortality globally, particularly in sub-Saharan Africa. Despite repeated exposure and vaccine deployment, sterile immunity against malaria rarely develops. Advances in malaria immunology over the past decades have revealed complex host-parasite interactions that shape clinical outcomes and inform new therapeutic strategies.

This narrative review aims to highlight the emerging role of monoclonal antibody interventions for malaria prevention.

Relevant articles were identified through a search of PubMed up to June 2026. Search terms included 'malaria immunology', 'Plasmodium falciparum', 'monoclonal antibodies', and 'immune correlates'. Additional references were identified from the bibliographies of relevant publications. Articles were selected based on relevance to clinical translation.

This review synthesizes evidence from primary immunology studies, translational research, clinical trials, and review articles to provide an updated overview of P. falciparum immunity and monoclonal antibody-based interventions. It highlights key immunological mechanisms and biomarkers associated with protective immunity, including functional antibody responses, cell-mediated immunity, cytokine regulation, and immune memory. It further summarizes the clinical development of leading monoclonal antibodies, including CIS43LS, L9LS, MAM01, and TB31F, which have demonstrated favourable safety profiles, prolonged serum half-lives, and high levels of protection against P. falciparum infection in controlled human malaria infection and field trials. The findings support monoclonal antibodies as promising tools for malaria prevention.

Current evidence indicates that long-acting monoclonal antibodies have the potential to complement existing malaria control strategies by providing rapid, highly effective, and durable protection, particularly for populations at greatest risk of infection, including young children, pregnant women, and individuals in seasonal transmission settings. Continued optimization of antibody potency, durability, and delivery platforms, together with the identification of robust immune correlates of protection, will be critical for integrating monoclonal antibodies into future malaria control programs.