9ye2 | pdb_00009ye2
Crystal Structure of the GRAM-4 antibody fragment in complex with NAGG peptide
Structural highlights
Publication Abstract from PubMedCircumsporozoite protein (CSP) is the most abundant Plasmodium sporozoite surface antigen. It is the major component of licensed Plasmodium falciparum vaccines and, hence, is the logical lead candidate for Plasmodium vivax (P. vivax) vaccines. However, our limited knowledge of protective B cell epitopes on P. vivax CSP remains a major roadblock. Here we identified two Plasmodium vivax CSP (PvCSP) B cell epitopes, PvCSP-A and PvCSP-B/NAGG, by screening inhibitory plasma from P. vivax-infected individuals. The epitopes were located in the N- and C-terminal regions of PvCSP, respectively, and were distinct from the canonical central repeat region epitope. We isolated a monoclonal antibody, GRAM-4, that recognized the PvCSP-B/NAGG epitope and mediated potent inhibition of traversal, hepatocyte invasion, and liver-stage development in vitro, confirming PvCSP-B/NAGG as a genuine neutralization target. Structural resolution of the GRAM-4:PvCSP-B/NAGG interaction at 2.65 A revealed the molecular basis of epitope recognition, providing a blueprint for PvCSP vaccine development. Targeting a site of vulnerability on circumsporozoite protein inhibits Plasmodium vivax malaria infection.,Visweswaran GRR, Mahdavi P, Vijayan K, Ntumngia FB, Staker BL, Barnes SJ, Subramani PA, Raappana A, Dambrauskas N, Glennon EKK, Kolli SK, Ogbondah MM, Watson A, Camargo N, Sankaran B, Thawornpan P, Jenwithisuk R, Myler PJ, Kappe SHI, Roobsoong W, Chootong P, Sattabongkot J, Kaushansky A, Vigdorovich V, Adams JH, Sather DN Immunity. 2026 Sep 24:S1074-7613(26)00376-6. doi: 10.1016/j.immuni.2026.09.001. PMID:42785294[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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