9OSX

PfCyRPA-EM epitope mimic bound to monoclonal antibody Cy.004

Summary for 9OSX

• Entry DOI: 10.2210/pdb9osx/pdb
• Descriptor: PfCyRPA-EM, Cy.004 heavy chain, Cy.004 light chain, ... (4 entities in total)
• Functional Keywords: pfcyrpa, blood-stage malaria, vaccine immunogen design, immune system
• Biological source: synthetic construct; More
• Total number of polymer chains: 3
• Total formula weight: 71868.75

Authors

Alam, N.,Higgins, M.K. (deposition date: 2025-05-26, release date: 2025-12-24, Last modification date: 2026-03-25)

Primary citation

Alam, N.,Wolfle, C.,Butkeviciute, E.,Quinkert, D.,King, L.D.W.,Higgins, M.K.
Structure-guided design of a PfCyRPA-based vaccine against blood-stage malaria.
Embo Mol Med, 18:873-890, 2026

PubMed Abstract: Effective vaccines against malaria are urgently required. All components of the PfPCRCR complex are essential for erythrocyte invasion by Plasmodium falciparum and are potential vaccine immunogens against blood-stage malaria. Of these, PfRH5 has progressed furthest in clinical development, while PfCyRPA also induces parasite growth-inhibitory antibodies. Here, we used direct nanoparticle coupling and structure-guided design to generate improved PfCyRPA-based immunogens. PfCyRPA is a six-bladed β-propeller. Blades 1 and 2 are exposed in the PfPCRCR complex and contain the epitopes of the most potent known growth-inhibitory antibodies. We therefore performed structure-guided design to generate a correctly folded, thermostable epitope mimic, PfCyRPA-EM, containing blades 1 and 2. In a pre-clinical model, PfCyRPA-EM elicited antibodies that inhibited parasite growth at lower concentrations than those elicited by PfCyRPA. In addition, the higher thermostability of PfCyRPA-EM and its improved expression as an I53-50 nanoparticle fusion make it well-suited for clinical development, alone or with other immunogens.

PubMed: 41772083
DOI: 10.1038/s44321-026-00376-x

Experimental method

X-RAY DIFFRACTION (2.67 Å)