7rqp
Structure of PfCSP NPNV binding antibody L9
Structural highlights
Publication Abstract from PubMedL9 is a potent human monoclonal antibody (mAb) that preferentially binds two adjacent NVDP minor repeats and cross-reacts with NANP major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) on malaria-infective sporozoites. Understanding this mAb's ontogeny and mechanisms of binding PfCSP will facilitate vaccine development. Here, we isolate mAbs clonally related to L9 and show that this B cell lineage has baseline NVDP affinity and evolves to acquire NANP reactivity. Pairing the L9 kappa light chain (L9kappa) with clonally related heavy chains results in chimeric mAbs that cross-link two NVDPs, cross-react with NANP, and more potently neutralize sporozoites in vivo compared with their original light chain. Structural analyses reveal that the chimeric mAbs bound minor repeats in a type-1 beta-turn seen in other repeat-specific antibodies. These data highlight the importance of L9kappa in binding NVDP on PfCSP to neutralize sporozoites and suggest that PfCSP-based immunogens might be improved by presenting >/=2 NVDPs. The light chain of the L9 antibody is critical for binding circumsporozoite protein minor repeats and preventing malaria.,Wang LT, Hurlburt NK, Schon A, Flynn BJ, Flores-Garcia Y, Pereira LS, Kiyuka PK, Dillon M, Bonilla B, Zavala F, Idris AH, Francica JR, Pancera M, Seder RA Cell Rep. 2022 Feb 15;38(7):110367. doi: 10.1016/j.celrep.2022.110367. PMID:35172158[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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