Broadly protective protein-based pneumococcal vaccine composed of pneumolysin toxoid-CbpA peptide recombinant fusion protein

J Infect Dis. 2014 Apr 1;209(7):1116-25. doi: 10.1093/infdis/jit502. Epub 2013 Sep 16.

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.

Keywords: Streptococcus pneumoniae; meningitis; meningococcus; pneumonia; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Carrier State / prevention & control*
  • Cross Protection
  • Disease Models, Animal
  • Female
  • Haemophilus influenzae / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neisseria meningitidis / immunology
  • Pneumococcal Infections / prevention & control*
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / genetics
  • Pneumococcal Vaccines / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Streptococcus pneumoniae / immunology
  • Streptolysins / genetics
  • Streptolysins / immunology*
  • Toxoids / genetics
  • Toxoids / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • CbpA protein, bacteria
  • Pneumococcal Vaccines
  • Recombinant Fusion Proteins
  • Streptolysins
  • Toxoids
  • Vaccines, Synthetic
  • plY protein, Streptococcus pneumoniae