Peptide mimics of the group B meningococcal capsule induce bactericidal and protective antibodies after immunization

J Immunol. 2007 Apr 1;178(7):4417-23. doi: 10.4049/jimmunol.178.7.4417.

Abstract

Neisseria meningitidis serogroup B (MenB) is a leading cause of sepsis and meningitis in children. No vaccine is available for the prevention of these infections because the group B capsular polysaccharide (CP) (MenB CP) is unable to stimulate an immune response, due to its similarity with human polysialic acid. Because the MenB CP bears both human cross-reactive and non-cross-reactive determinants, we developed immunogenic peptide mimics of the latter epitopes. Peptides were selected from phage display libraries for their ability to bind to a protective anti-MenB CP mAb. One of these peptides (designated 9M) induced marked elevations in serum bactericidal activity, but not polysialic acid cross-reacting Abs, after gene priming followed by carrier-conjugate boosting. Moreover, the occurrence of bacteremia was prevented in infant rats by administration of immune sera before MenB challenge. 9M is a promising lead candidate for the development of an effective and affordable anti-MenB vaccine.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Monoclonal / immunology
  • Bacteremia / prevention & control*
  • Bacterial Capsules
  • DNA / genetics
  • Immune Sera / immunology
  • Immunization
  • Immunization, Passive
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Mimicry*
  • Molecular Sequence Data
  • Neisseria meningitidis, Serogroup B*
  • Peptide Library
  • Peptides / genetics
  • Peptides / immunology*
  • Peptides / pharmacology
  • Plasmids / genetics
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / immunology*
  • Rats
  • Rats, Inbred BB

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Immune Sera
  • Meningococcal Vaccines
  • Peptide Library
  • Peptides
  • Polysaccharides, Bacterial
  • capsular polysaccharide, meningococcal group B
  • peptide 9M
  • DNA