title: Sequence- and Structure-Based Immunoreactive Epitope Discovery for Burkholderia pseudomallei Flagellin.
abstract: Burkholderia pseudomallei is a Gram-negative bacterium responsible for melioidosis, a serious and often fatal infectious disease that is poorly controlled by existing treatments. Due to its inherent resistance to the major antibiotic classes and its facultative intracellular pathogenicity, an effective vaccine would be extremely desirable, along with appropriate prevention and therapeutic management. One of the main subunit vaccine candidates is flagellin of Burkholderia pseudomallei (FliCBp). Here, we present the high resolution crystal structure of FliCBp and report the synthesis and characterization of three peptides predicted to be both B and T cell FliCBp epitopes, by both structure-based in silico methods, and sequence-based epitope prediction tools. All three epitopes were shown to be immunoreactive against human IgG antibodies and to elicit cytokine production from human peripheral blood mononuclear cells. Furthermore, two of the peptides (F51-69 and F270-288) were found to be dominant immunoreactive epitopes, and their antibodies enhanced the bactericidal activities of purified human neutrophils. The epitopes derived from this study may represent potential melioidosis vaccine components.
authors.affiliation: The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Arnone
authors.initials: A
authors.lastname: Nithichanon
authors.affiliation: The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Darawan
authors.initials: D
authors.lastname: Rinchai
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gori
authors.affiliation: Department of Biosciences, CIMAINA and CNR Institute of Biophysics, University of Milan, Milan, Italy.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lassaux
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Peri
authors.affiliation: Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Conchillio-Solé
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Ferrer-Navarro
authors.affiliation: Department of Biosciences, CIMAINA and CNR Institute of Biophysics, University of Milan, Milan, Italy.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Gourlay
authors.affiliation: Department of Biosciences, CIMAINA and CNR Institute of Biophysics, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Nardini
authors.affiliation: Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Bellaterra, Spain; Catalan Institution for Research and Advanced Studies, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.affiliation: Department of Biosciences, CIMAINA and CNR Institute of Biophysics, University of Milan, Milan, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.affiliation: The Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Ganjana
authors.initials: G
authors.lastname: Lertmemonkolchai
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005408:Flagellin / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008554:Melioidosis / Q000276:immunology / Q000382:microbiology*; D008969:Molecular Sequence Data; D010587:Phagocytosis; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005408:Flagellin