title: Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology.
abstract: We solved the crystal structure of Burkholderia pseudomallei acute phase antigen BPSL2765 in the context of a structural vaccinology study, in the area of melioidosis vaccine development. Based on the structure, we applied a recently developed method for epitope design that combines computational epitope predictions with in vitro mapping experiments and successfully identified a consensus sequence within the antigen that, when engineered as a synthetic peptide, was selectively immunorecognized to the same extent as the recombinant protein in sera from melioidosis-affected subjects. Antibodies raised against the consensus peptide were successfully tested in opsonization bacterial killing experiments and antibody-dependent agglutination tests of B. pseudomallei. Our strategy represents a step in the development of immunodiagnostics, in the production of specific antibodies and in the optimization of antigens for vaccine development, starting from structural and physicochemical principles.
authors.affiliation: Department of Biosciences, University of Milan, 20133 Milan, Italy.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Gourlay
authors.forename: Claudio
authors.initials: C
authors.lastname: Peri
authors.forename: Mario
authors.initials: M
authors.lastname: Ferrer-Navarro
authors.forename: Oscar
authors.initials: O
authors.lastname: Conchillo-Solé
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gori
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Thomas
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Champion
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Michell
authors.forename: Chidchamai
authors.initials: C
authors.lastname: Kewcharoenwong
authors.forename: Arnone
authors.initials: A
authors.lastname: Nithichanon
authors.forename: Patricia
authors.initials: P
authors.lastname: Lassaux
authors.forename: Lucia
authors.initials: L
authors.lastname: Perletti
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemongkolchai
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000378:metabolism; D018360:Crystallography, X-Ray; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology
chemical_list: D000906:Antibodies; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D011994:Recombinant Proteins