title: Serum reactome induced by Bordetella pertussis infection and Pertussis vaccines: qualitative differences in serum antibody recognition patterns revealed by peptide microarray analysis.
abstract: BACKGROUND
  Pertussis (whooping cough) remains a public health problem despite extensive vaccination strategies. Better understanding of the host-pathogen interaction and the detailed B. pertussis (Bp) target recognition pattern will help in guided vaccine design. We characterized the specific epitope antigen recognition profiles of serum antibodies ('the reactome') induced by whooping cough and B. pertussis (Bp) vaccines from a case-control study conducted in 1996 in infants enrolled in a Bp vaccine trial in Sweden (Gustafsson, NEJM, 1996, 334, 349-355).
  
  
  METHODS
  Sera from children with whooping cough, vaccinated with Diphtheria Tetanus Pertussis (DTP) whole-cell (wc), acellular 5 (DPTa5), or with the 2 component (a2) vaccines and from infants receiving only DT (n=10 for each group) were tested with high-content peptide microarrays containing 17 Bp proteins displayed as linear (n=3175) peptide stretches. Slides were incubated with serum and peptide-IgG complexes detected with Cy5-labeled goat anti-human IgG and analyzed using a GenePix 4000B microarray scanner, followed by statistical analysis, using PAM (Prediction Analysis for Microarrays) and the identification of uniquely recognized peptide epitopes.
  
  
  RESULTS
  367/3,085 (11.9%) peptides were recognized in 10/10 sera from children with whooping cough, 239 (7.7%) in DTPwc, 259 (8.4%) in DTPa5, 105 (3.4%) DTPa2, 179 (5.8%) in the DT groups. Recognition of strongly recognized peptides was similar between whooping cough and DPTwc, but statistically different between whooping cough vs. DTPa5 (p<0.05), DTPa2 and DT (p<0.001 vs. both) vaccines. 6/3,085 and 2/3,085 peptides were exclusively recognized in (10/10) sera from children with whooping cough and DTPa2 vaccination, respectively. DTPwc resembles more closely the whooping cough reactome as compared to acellular vaccines.
  
  
  CONCLUSIONS
  We could identify a unique recognition signature common for each vaccination group (10/10 children). Peptide microarray technology allows detection of subtle differences in epitope signature responses and may help to guide rational vaccine development by the objective description of a clinically relevant immune response that confers protection against infectious pathogens.
authors.affiliation: Center for allogeneic stem cell transplantation, Karolinska University Hospital, Huddinge, Sweden. Davide.Valentini@ki.se.|Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. Davide.Valentini@ki.se.
authors.forename: Davide
authors.initials: D
authors.lastname: Valentini
authors.affiliation: Lung Allergi Kliniken, Karolinska University Hospital, Stockholm, Sweden. Giovanni.Ferrara@ki.se.|Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Giovanni.Ferrara@ki.se.|Department of Medicine, University of Perugia, Perugia, Italy. Giovanni.Ferrara@ki.se.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrara
authors.affiliation: The Swedish National Institute of Public Health, Solna, Sweden. Reza.Advani@folkhalsomyndigheten.se.
authors.forename: Reza
authors.initials: R
authors.lastname: Advani
authors.affiliation: The Swedish National Institute of Public Health, Solna, Sweden. Hans.Hallander@gmail.com.
authors.forename: Hans O
authors.initials: HO
authors.lastname: Hallander
authors.affiliation: Center for allogeneic stem cell transplantation, Karolinska University Hospital, Huddinge, Sweden. markus.maeurer@ki.se.|Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. markus.maeurer@ki.se.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood*; D001886:Bordetella pertussis / Q000276:immunology*; D002648:Child; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010567:Pertussis Vaccine / Q000276:immunology*; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome / Q000378:metabolism; D014611:Vaccination; D014917:Whooping Cough / Q000097:blood* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D010455:Peptides; D010567:Pertussis Vaccine; D020543:Proteome