title: Molecular Engineering of Ghfp, the Gonococcal Orthologue of Neisseria meningitidis Factor H Binding Protein.
abstract: Knowledge of the sequences and structures of proteins produced by microbial pathogens is continuously increasing. Besides offering the possibility of unraveling the mechanisms of pathogenesis at the molecular level, structural information provides new tools for vaccine development, such as the opportunity to improve viral and bacterial vaccine candidates by rational design. Structure-based rational design of antigens can optimize the epitope repertoire in terms of accessibility, stability, and variability. In the present study, we used epitope mapping information on the well-characterized antigen of Neisseria meningitidis factor H binding protein (fHbp) to engineer its gonococcal homologue, Ghfp. Meningococcal fHbp is typically classified in three distinct antigenic variants. We introduced epitopes of fHbp variant 1 onto the surface of Ghfp, which is naturally able to protect against meningococcal strains expressing fHbp of variants 2 and 3. Heterologous epitopes were successfully transplanted, as engineered Ghfp induced functional antibodies against all three fHbp variants. These results confirm that structural vaccinology represents a successful strategy for modulating immune responses, and it is a powerful tool for investigating the extension and localization of immunodominant epitopes.
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rippa
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Santini
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lo Surdo
authors.affiliation: Centro Risonanze Magnetiche (CERM) and Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cantini
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Veggi
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Gentile
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Grassi
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Iannello
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Brunelli
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferlicca
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Palmieri
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Pallaoro
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Aricò
authors.affiliation: Centro Risonanze Magnetiche (CERM) and Department of Chemistry, University of Florence, Sesto Fiorentino, Italy banci@cerm.unifi.it maria.x.scarselli@gsk.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.affiliation: Novartis Vaccines Srl, a GSK Company, Siena, Italy banci@cerm.unifi.it maria.x.scarselli@gsk.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Scarselli
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D001770:Blood Bactericidal Activity; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000235:genetics* / Q000276:immunology*; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D037521:Virulence Factors; C484699:factor H-binding protein, Neisseria meningitidis