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Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody

Neisserial heparin binding antigen (NHBA) is one of three main recombinant protein antigens in 4CMenB, a vaccine for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B. NHBA is a surface-exposed lipoprotein composed of a predicted disordered N-terminal regi...

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Autores principales: Maritan, Martina, Veggi, Daniele, Cozzi, Roberta, Dello Iacono, Lucia, Bartolini, Erika, Lo Surdo, Paola, Maruggi, Giulietta, Spraggon, Glen, Bottomley, Matthew J., Malito, Enrico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104945/
https://www.ncbi.nlm.nih.gov/pubmed/30133484
http://dx.doi.org/10.1371/journal.pone.0201922
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author Maritan, Martina
Veggi, Daniele
Cozzi, Roberta
Dello Iacono, Lucia
Bartolini, Erika
Lo Surdo, Paola
Maruggi, Giulietta
Spraggon, Glen
Bottomley, Matthew J.
Malito, Enrico
author_facet Maritan, Martina
Veggi, Daniele
Cozzi, Roberta
Dello Iacono, Lucia
Bartolini, Erika
Lo Surdo, Paola
Maruggi, Giulietta
Spraggon, Glen
Bottomley, Matthew J.
Malito, Enrico
author_sort Maritan, Martina
collection PubMed
description Neisserial heparin binding antigen (NHBA) is one of three main recombinant protein antigens in 4CMenB, a vaccine for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B. NHBA is a surface-exposed lipoprotein composed of a predicted disordered N-terminal region, an arginine-rich region that binds heparin, and a C-terminal domain that folds as an anti-parallel β-barrel and that upon release after cleavage by human proteases alters endothelial permeability. NHBA induces bactericidal antibodies in humans, and NHBA-specific antibodies elicited by the 4CMenB vaccine contribute to serum bactericidal activity, the correlate of protection. To better understand the structural bases of the human antibody response to 4CMenB vaccination and to inform antigen design, we used X-ray crystallography to elucidate the structures of two C-terminal fragments of NHBA, either alone or in complex with the Fab derived from the vaccine-elicited human monoclonal antibody 5H2, and the structure of the unbound Fab 5H2. The structures reveal details on the interaction between an N-terminal β-hairpin fragment and the β-barrel, and explain how NHBA is capable of generating cross-reactive antibodies through an extensive conserved conformational epitope that covers the entire C-terminal face of the β-barrel. By providing new structural information on a vaccine antigen and on the human immune response to vaccination, these results deepen our molecular understanding of 4CMenB, and might also aid future vaccine design projects.
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spelling pubmed-61049452018-09-15 Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody Maritan, Martina Veggi, Daniele Cozzi, Roberta Dello Iacono, Lucia Bartolini, Erika Lo Surdo, Paola Maruggi, Giulietta Spraggon, Glen Bottomley, Matthew J. Malito, Enrico PLoS One Research Article Neisserial heparin binding antigen (NHBA) is one of three main recombinant protein antigens in 4CMenB, a vaccine for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B. NHBA is a surface-exposed lipoprotein composed of a predicted disordered N-terminal region, an arginine-rich region that binds heparin, and a C-terminal domain that folds as an anti-parallel β-barrel and that upon release after cleavage by human proteases alters endothelial permeability. NHBA induces bactericidal antibodies in humans, and NHBA-specific antibodies elicited by the 4CMenB vaccine contribute to serum bactericidal activity, the correlate of protection. To better understand the structural bases of the human antibody response to 4CMenB vaccination and to inform antigen design, we used X-ray crystallography to elucidate the structures of two C-terminal fragments of NHBA, either alone or in complex with the Fab derived from the vaccine-elicited human monoclonal antibody 5H2, and the structure of the unbound Fab 5H2. The structures reveal details on the interaction between an N-terminal β-hairpin fragment and the β-barrel, and explain how NHBA is capable of generating cross-reactive antibodies through an extensive conserved conformational epitope that covers the entire C-terminal face of the β-barrel. By providing new structural information on a vaccine antigen and on the human immune response to vaccination, these results deepen our molecular understanding of 4CMenB, and might also aid future vaccine design projects. Public Library of Science 2018-08-22 /pmc/articles/PMC6104945/ /pubmed/30133484 http://dx.doi.org/10.1371/journal.pone.0201922 Text en © 2018 Maritan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Maritan, Martina
Veggi, Daniele
Cozzi, Roberta
Dello Iacono, Lucia
Bartolini, Erika
Lo Surdo, Paola
Maruggi, Giulietta
Spraggon, Glen
Bottomley, Matthew J.
Malito, Enrico
Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody
title Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody
title_full Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody
title_fullStr Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody
title_full_unstemmed Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody
title_short Structures of NHBA elucidate a broadly conserved epitope identified by a vaccine induced antibody
title_sort structures of nhba elucidate a broadly conserved epitope identified by a vaccine induced antibody
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104945/
https://www.ncbi.nlm.nih.gov/pubmed/30133484
http://dx.doi.org/10.1371/journal.pone.0201922
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