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5o14
From Proteopedia
Co-crystal structure of a cross-reactive bactericidal human antibody targeting meningococcal vaccine antigen factor H binding protein
Structural highlights
FunctionFHBP_NEIMB A bacterial surface lipoprotein that binds host (human) complement factor H (fH, gene CFH), binding contributes to the avoidance of complement-mediated lysis by N.meningitidis. Binding of fH to the bacteria surface is independent of bacterial sialic acid moieties (PubMed:16751403). fH binding affinity is high enough that it may sequester plasma fH, depleting its circulating levels and de-regulating complement in the host (Probable). This protein induces high levels of bactericidal antibodies in mice (PubMed:12642606, PubMed:15039331, PubMed:15664958, PubMed:21753121, PubMed:23133374).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedData obtained recently in the United Kingdom following a nationwide infant immunization program against serogroup B Neisseria meningitidis (MenB) reported >80% 4CMenB vaccine-mediated protection. Factor H-binding protein (fHbp) is a meningococcal virulence factor and a component of two new MenB vaccines. Here, we investigated the structural bases underlying the fHbp-dependent protective antibody response in humans, which might inform future antigen design efforts. We present the co-crystal structure of a human antibody Fab targeting fHbp. The vaccine-elicited Fab 1A12 is cross-reactive and targets an epitope highly conserved across the repertoire of three naturally occurring fHbp variants. The free Fab structure highlights conformational rearrangements occurring upon antigen binding. Importantly, 1A12 is bactericidal against MenB strains expressing fHbp from all three variants. Our results reveal important immunological features potentially contributing to the broad protection conferred by fHbp vaccination. Our studies fuel the rationale of presenting conserved protein epitopes when developing broadly protective vaccines. Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp.,Lopez-Sagaseta J, Beernink PT, Bianchi F, Santini L, Frigimelica E, Lucas AH, Pizza M, Bottomley MJ Nat Commun. 2018 Feb 6;9(1):528. doi: 10.1038/s41467-018-02827-7. PMID:29410413[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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