Protective immunization against group B meningococci using anti-idiotypic mimics of the capsular polysaccharide

J Immunol. 2004 Feb 15;172(4):2461-8. doi: 10.4049/jimmunol.172.4.2461.

Abstract

Use of the serogroup B meningococcal capsular polysaccharide (MenB CP) as a vaccine is hampered by the presence of epitopes that cross-react with human polysialic acid. As non-cross-reactive, protective capsular epitopes have also been described, we set out to develop protein mimics of one of such epitopes using as a template a highly protective mAb (mAb Seam 3) raised against a chemically modified form of the MenB CP (N-Pr MenB CP). Using phage display, anti-idiotypic single-chain Ab fragments (scFvs) were obtained from spleen cells of mice immunized with the Seam 3 mAb. Two Seam 3-specific scFvs competed with N-Pr MenB CP for binding to either mAb Seam 3 or rabbit Abs present in typing sera. Moreover, in mice and rabbits the scFvs elicited the production of Abs reacting with both N-Pr MenB CP and whole meningococci, but not with human polysialic acid. These scFv-induced Ab responses were boostable and of the Th1 type, as shown by a predominance of IgG2a. In addition, passive immunization with sera from scFv-immunized animals partially protected neonatal mice from experimental infection with group B meningococci. In conclusion, we have produced anti-idiotypic scFvs that mimic a protective MenB CP epitope and may be useful in the development of an alternative group B meningococcal vaccine.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / administration & dosage*
  • Antibodies, Anti-Idiotypic / biosynthesis
  • Antibodies, Anti-Idiotypic / metabolism
  • Antibodies, Bacterial / biosynthesis
  • Bacterial Capsules
  • Binding Sites, Antibody
  • Binding, Competitive / immunology
  • Blood Bactericidal Activity
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunization, Passive
  • Immunoglobulin Variable Region / biosynthesis
  • Immunoglobulin Variable Region / metabolism
  • Meningococcal Infections / immunology
  • Meningococcal Infections / mortality
  • Meningococcal Infections / prevention & control
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Mimicry / immunology*
  • Molecular Sequence Data
  • Neisseria meningitidis / classification*
  • Neisseria meningitidis / growth & development
  • Neisseria meningitidis / immunology*
  • Opsonin Proteins / blood
  • Polysaccharides, Bacterial / immunology*
  • Rabbits
  • Single-Chain Antibodies

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Bacterial
  • Immunoglobulin Variable Region
  • Meningococcal Vaccines
  • Opsonin Proteins
  • Polysaccharides, Bacterial
  • Single-Chain Antibodies
  • capsular polysaccharide, meningococcal group B
  • scFv 421

Associated data

  • GENBANK/AY374127
  • GENBANK/AY374128