6o2b
Crystal structure of 4493 Fab in complex with circumsporozoite protein DND and anti-kappa VHH domainCrystal structure of 4493 Fab in complex with circumsporozoite protein DND and anti-kappa VHH domain
Structural highlights
Publication Abstract from PubMedThe circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanisms driving the development of the most potent human PfCSP antibodies and identification of their target epitopes. By characterizing 200 human monoclonal PfCSP antibodies induced by sporozoite immunization, we establish that the most potent antibodies bind around a conserved (N/D)PNANPN(V/A) core. High antibody affinity to the core correlates with protection from parasitemia in mice and evolves around the recognition of NANP motifs. The data suggest that the rational design of a next-generation PfCSP vaccine that elicits high-affinity antibody responses against the core epitope will promote the induction of protective humoral immune responses. Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs.,Murugan R, Scally SW, Costa G, Mustafa G, Thai E, Decker T, Bosch A, Prieto K, Levashina EA, Julien JP, Wardemann H Nat Med. 2020 May 25. pii: 10.1038/s41591-020-0881-9. doi:, 10.1038/s41591-020-0881-9. PMID:32451496[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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