title: Broadly protective protein-based pneumococcal vaccine composed of pneumolysin toxoid-CbpA peptide recombinant fusion protein.
abstract: BACKGROUND
  Pneumococcus, meningococcus, and Haemophilus influenzae cause a similar spectrum of infections in the ear, lung, blood, and brain. They share cross-reactive antigens that bind to the laminin receptor of the blood-brain barrier as a molecular basis for neurotropism, and this step in pathogenesis was addressed in vaccine design.
  
  
  METHODS
  Biologically active peptides derived from choline-binding protein A (CbpA) of pneumococcus were identified and then genetically fused to L460D pneumolysoid. The fusion construct was tested for vaccine efficacy in mouse models of nasopharyngeal carriage, otitis media, pneumonia, sepsis, and meningitis.
  
  
  RESULTS
  The CbpA peptide-L460D pneumolysoid fusion protein was more broadly immunogenic than pneumolysoid alone, and antibodies were active in vitro against Streptococcus pneumoniae, Neisseria meningitidis, and H. influenzae. Passive and active immunization protected mice from pneumococcal carriage, otitis media, pneumonia, bacteremia, meningitis, and meningococcal sepsis.
  
  
  CONCLUSIONS
  The CbpA peptide-L460D pneumolysoid fusion protein was broadly protective against pneumococcal infection, with the potential for additional protection against other meningeal pathogens.
authors.affiliation: Department of Infectious Diseases.
authors.forename: Beth
authors.initials: B
authors.lastname: Mann
authors.forename: Justin
authors.initials: J
authors.lastname: Thornton
authors.forename: Richard
authors.initials: R
authors.lastname: Heath
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Wade
authors.forename: Rodney K
authors.initials: RK
authors.lastname: Tweten
authors.forename: Geli
authors.initials: G
authors.lastname: Gao
authors.forename: Karim
authors.initials: K
authors.lastname: El Kasmi
authors.forename: John B
authors.initials: JB
authors.lastname: Jordan
authors.forename: Diana M
authors.initials: DM
authors.lastname: Mitrea
authors.forename: Richard
authors.initials: R
authors.lastname: Kriwacki
authors.forename: Jeff
authors.initials: J
authors.lastname: Maisonneuve
authors.forename: Mark
authors.initials: M
authors.lastname: Alderson
authors.forename: Elaine I
authors.initials: EI
authors.lastname: Tuomanen
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002353:Carrier State / Q000517:prevention & control*; D056738:Cross Protection; D004195:Disease Models, Animal; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009345:Neisseria meningitidis / Q000276:immunology; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D013301:Streptolysins / Q000235:genetics / Q000276:immunology*; D014121:Toxoids / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; C490083:CbpA protein, bacteria; D022242:Pneumococcal Vaccines; D011993:Recombinant Fusion Proteins; D013301:Streptolysins; D014121:Toxoids; D014614:Vaccines, Synthetic; C032290:plY protein, Streptococcus pneumoniae
keywords: Streptococcus pneumoniae; meningitis; meningococcus; pneumonia; vaccine
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