Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice

Vaccine. 2007 Oct 10;25(41):7247-60. doi: 10.1016/j.vaccine.2007.07.038. Epub 2007 Aug 6.

Abstract

We have previously demonstrated the full-length gonococcal transferrin binding proteins (TbpA and TbpB) to be promising antigens in the development of a protective vaccine against Neisseria gonorrhoeae. In the current study we employed a genetic chimera approach fusing domains from TbpA and TbpB to the A2 domain of cholera toxin, which naturally binds in a non-covalent fashion to the B subunit of cholera toxin during assembly. For one construct, the N-terminal half of TbpB (NB) was fused to the A2 subunit of cholera toxin. In a second construct, the loop 2 region (L2) of TbpA was genetically fused between the NB domain and the A2 domain, generating a double chimera. Both chimeras were immunogenic and induced serum bactericidal and vaginal growth-inhibiting antibodies. This study highlights the potential of using protective epitopes instead of full-length proteins in the development of an efficacious gonococcal vaccine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / immunology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Cholera Toxin / chemistry
  • Cholera Toxin / genetics
  • Cholera Toxin / immunology
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Female
  • Gonorrhea / immunology
  • Gonorrhea / prevention & control*
  • Mice
  • Microbial Viability / immunology*
  • Molecular Sequence Data
  • Neisseria gonorrhoeae / growth & development*
  • Neisseria gonorrhoeae / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Sequence Analysis, DNA
  • Transferrin-Binding Protein A / chemistry
  • Transferrin-Binding Protein A / genetics
  • Transferrin-Binding Protein A / immunology*
  • Transferrin-Binding Protein B / chemistry
  • Transferrin-Binding Protein B / genetics
  • Transferrin-Binding Protein B / immunology*
  • Vagina / microbiology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • DNA, Bacterial
  • Recombinant Fusion Proteins
  • Transferrin-Binding Protein A
  • Transferrin-Binding Protein B
  • Cholera Toxin

Associated data

  • GENBANK/EF547129
  • GENBANK/EF547130