| Structural highlights
Function
FHBP_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 PubMed
Data 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
- ↑ Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J, Arico B, Brunelli B, Pieri A, Santini L, Savino S, Serruto D, Litt D, Kroll S, Welsch JA, Granoff DM, Rappuoli R, Pizza M. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med. 2003 Mar 17;197(6):789-99. PMID:12642606 doi:10.1084/jem.20021911
- ↑ Fletcher LD, Bernfield L, Barniak V, Farley JE, Howell A, Knauf M, Ooi P, Smith RP, Weise P, Wetherell M, Xie X, Zagursky R, Zhang Y, Zlotnick GW. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun. 2004 Apr;72(4):2088-100. PMID:15039331 doi:10.1128/IAI.72.4.2088-2100.2004
- ↑ Giuliani MM, Santini L, Brunelli B, Biolchi A, Aricò B, Di Marcello F, Cartocci E, Comanducci M, Masignani V, Lozzi L, Savino S, Scarselli M, Rappuoli R, Pizza M. The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun. 2005 Feb;73(2):1151-60. PMID:15664958 doi:10.1128/IAI.73.2.1151-1160.2005
- ↑ Schneider MC, Exley RM, Chan H, Feavers I, Kang YH, Sim RB, Tang CM. Functional significance of factor H binding to Neisseria meningitidis. J Immunol. 2006 Jun 15;176(12):7566-75. PMID:16751403 doi:10.4049/jimmunol.176.12.7566
- ↑ Scarselli M, Arico B, Brunelli B, Savino S, Di Marcello F, Palumbo E, Veggi D, Ciucchi L, Cartocci E, Bottomley MJ, Malito E, Lo Surdo P, Comanducci M, Giuliani MM, Cantini F, Dragonetti S, Colaprico A, Doro F, Giannetti P, Pallaoro M, Brogioni B, Tontini M, Hilleringmann M, Nardi-Dei V, Banci L, Pizza M, Rappuoli R. Rational design of a meningococcal antigen inducing broad protective immunity. Sci Transl Med. 2011 Jul 13;3(91):91ra62. PMID:21753121 doi:10.1126/scitranslmed.3002234
- ↑ Johnson S, Tan L, van der Veen S, Caesar J, Goicoechea De Jorge E, Harding RJ, Bai X, Exley RM, Ward PN, Ruivo N, Trivedi K, Cumber E, Jones R, Newham L, Staunton D, Ufret-Vincenty R, Borrow R, Pickering MC, Lea SM, Tang CM. Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules. PLoS Pathog. 2012 Oct;8(10):e1002981. doi: 10.1371/journal.ppat.1002981. Epub, 2012 Oct 25. PMID:23133374 doi:http://dx.doi.org/10.1371/journal.ppat.1002981
- ↑ Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769
- ↑ Lopez-Sagaseta J, Beernink PT, Bianchi F, Santini L, Frigimelica E, Lucas AH, Pizza M, Bottomley MJ. Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp. Nat Commun. 2018 Feb 6;9(1):528. doi: 10.1038/s41467-018-02827-7. PMID:29410413 doi:http://dx.doi.org/10.1038/s41467-018-02827-7
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