A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40020675.
- Also identified by DOI 10.1016/j.xcrm.2025.101985 and PMC identifier 11970402.
- Licence recorded as CC BY-NC-ND.
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Abstract
Plasmodium falciparum apical membrane antigen 1 (AMA1) binds a loop in rhoptry neck protein 2 (RON2L) during red cell invasion and is a target for vaccines and therapeutic antibodies against malaria. Here, we report a panel of AMA1-specific naturally acquired human monoclonal antibodies (hmAbs) derived from individuals living in malaria-endemic regions. Two neutralizing hmAbs engage AMA1 independent of the RON2L-binding site. The hmAb 75B10 demonstrates potent strain-transcending neutralization that is independent of RON2L blockade, emphasizing that epitopes outside the RON2L-binding site elicit broad protection against variant parasite strains. The combination of these hmAbs synergistically enhances parasite neutralization. Vaccination with a structure-based design (SBD1) that mimics the AMA1-RON2L complex elicited antibodies similar to the two neutralizing hmAbs connecting vaccination to naturally acquired immunity in humans. The structural definition of a strain-transcending epitope on AMA1 targeted by naturally acquired hmAb establishes paradigms for developing AMA1-based vaccines and therapeutic antibodies.
Medical subject headings
- Antibodies, Monoclonal
- Plasmodium falciparum
- Protozoan Proteins
- Antibodies, Neutralizing
- Antigens, Protozoan
- Membrane Proteins
- Malaria, Falciparum
- Antibodies, Protozoan