title: Discovery of Immunodominant B Cell Epitopes within Surface Pneumococcal Virulence Proteins in Pediatric Patients with Invasive Pneumococcal Disease.
abstract: The identification of immunodominant B cell epitopes within surface pneumococcal virulence proteins in pediatric patients with invasive pneumococcal disease (IPD) is a valuable approach to define novel vaccine candidates. To this aim, we evaluated sera from children with IPD and age-matched controls against 141 20-mer synthetic peptides covering the entire sequence of major antigenic fragments within pneumococcal virulence proteins; namely, choline-binding protein D (CbpD), pneumococcal histidine triad proteins (PhtD and PhtE), pneumococcal surface protein A (PspA), plasminogen and fibronectin binding protein B (PfbB), and zinc metalloproteinase B (ZmpB). Ten immunodominant B cell epitopes were identified: CbpD-pep4 (amino acids (aa) 291-310), PhtD-pep11 (aa 88-107), PhtD-pep17 (aa 172-191), PhtD-pep19 (aa 200-219), PhtE-pep32 (aa 300-319), PhtE-pep40 (aa 79-98), PfbB-pep76 (aa 180-199), PfbB-pep79 (aa 222-241), PfbB-pep90 (aa 484-503), and ZmpB-pep125 (aa 431-450). All epitopes were highly conserved among different pneumococcal serotypes, and four of them were located within the functional zinc-binding domain of the histidine triad proteins PhtD and PhtE. Peptides CbpD-pep4, PhtD-pep19, and PhtE-pep40 were broadly recognized by IPD patient sera with prevalences of 96.4%, 92.9%, and 71.4%, respectively, whereas control sera exhibited only minor reactivities (<10.7%). Their specificities for IPD were 93.3%, 95%, and 96.7%; their sensitivities were 96.4%, 92.9%, and 71.4% and their positivity likelihood ratios for IPD were 14.5, 18.6, and 21.4, respectively. Furthermore, purified antibodies against CbpD-pep4, PhtD-pep19, and PhtE-pep40 readily bound on the surfaces of different pneumococcal serotypes, as assessed by FACS and immunofluorescence analysis. The identified immunodominant B cell epitopes provide a better understanding of immune response in IPD and are worth evaluation in additional studies as potential vaccine candidates.
authors.affiliation: From the First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA," and Departments of Microbiology and theanolagousi@hotmail.com theanolagousi@gmail.com.
authors.forename: Theano
authors.initials: T
authors.lastname: Lagousi
authors.affiliation: Departments of Microbiology and.
authors.forename: John
authors.initials: J
authors.lastname: Routsias
authors.affiliation: Biological Chemistry, Medical School, 11527 Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.affiliation: Departments of Microbiology and.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Tsakris
authors.affiliation: From the First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA," and.
authors.forename: George
authors.initials: G
authors.lastname: Chrousos
authors.affiliation: From the First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA," and.
authors.forename: Maria
authors.initials: M
authors.lastname: Theodoridou
authors.affiliation: From the First Department of Paediatrics, "Aghia Sophia" Children's Hospital, Immunobiology Research Laboratory and Infectious Diseases Department "MAKKA," and.
authors.forename: Vana
authors.initials: V
authors.lastname: Spoulou
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology; D000293:Adolescent; D000581:Amidohydrolases / Q000276:immunology; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D010455:Peptides; C078635:fibronectin-binding proteins, bacterial; C097552:histidine triad protein; D006867:Hydrolases; D000581:Amidohydrolases; C569012:CbpD protein, Streptococcus pneumoniae
keywords: Streptococcus; epitope mapping; pneumonia; vaccine development; zinc finger