Structure-guided design of a PfCyRPA-based vaccine against blood-stage malaria

Journal article

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.

Authors: Alam, N; Wolfle, C; Butkeviciute, E; Quinkert, D; King, LDW

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: EMBO Molecular Medicine
• Volume: 18
• Issue: 3
• Pages: 873-890
• Publication date: 2026-03-02
• Acceptance date: 2026-01-14
• DOI: 10.1038/s44321-026-00376-x
• EISSN: 1757-4684
• ISSN: 1757-4676
• Language: English
• Keywords: Malaria; Epitope; Antibody; Immune system; Thermostability; Plasmodium falciparum