2025/01/02 by Cherrelle Dacon, Re’em Moskovitz, Kristian E. Swearingen +44 · 2 voices
Immunology and Microbiology · Medicine · #HIV Research and Treatment #Malaria Research and Control #Mosquito-borne diseases and control
paper · doi:10.1126/science.adr0510
openalex publication_date 2025/01/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the Plasmodium falciparum circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines. MAD21-101, the most potent mAb in this class, confers sterile protection against Pf infection in a human liver–chimeric mouse model. These findings reveal a site of vulnerability on the sporozoite surface that can be targeted by next-generation antimalarial interventions.