Immunogenicity of synthetic saccharide fragments of Vibrio cholerae O1 (Ogawa and Inaba) bound to Exotoxin A

FEMS Immunol Med Microbiol. 2006 Nov;48(2):237-51. doi: 10.1111/j.1574-695X.2006.00143.x. Epub 2006 Sep 29.

Abstract

Recombinant exotoxin A (rEPA) from Pseudomonas aeruginosa conjugated to Vibrio cholerae O1 serotype-specific polysaccharides (mono-, di- and hexasaccharide) were immunogenic in mice. Monosaccharide conjugates boosted the humoral responses to the hexasaccharide conjugates. Prior exposure to purified Ogawa lipopolysaccharide (LPS) enabled contra-serotype hexasaccharide conjugates to boost the vibriocidal response, but Inaba LPS did not prime for an enhanced vibriocidal response by a contra-serotype conjugate. Prior exposure to the carrier, and priming B cells with the LPS of either serotype, resulted in enhanced vibriocidal titers if the Ogawa hexasaccharides were used, but a diminished response to the Inaba LPS. These studies demonstrate that the 'functional' B cell epitopes on the LPS differ from those of the neoglycoconjugates and that the order of immunization and the serotype of the boosting conjugate can influence the epitope specificity and function of the antisera.

Publication types

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

MeSH terms

  • ADP Ribose Transferases / chemistry
  • ADP Ribose Transferases / immunology*
  • ADP Ribose Transferases / pharmacology
  • Animals
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / immunology*
  • Bacterial Toxins / pharmacology
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cholera / immunology*
  • Cholera / microbiology
  • Cholera / prevention & control
  • Cholera / virology
  • Cholera Vaccines / chemistry
  • Cholera Vaccines / immunology*
  • Cholera Vaccines / pharmacology
  • Exotoxins / chemistry
  • Exotoxins / immunology*
  • Exotoxins / pharmacology
  • Female
  • Immunoconjugates / chemistry
  • Immunoconjugates / immunology*
  • Immunoconjugates / pharmacology
  • Immunoglobulin M / immunology
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oligosaccharides / chemistry
  • Oligosaccharides / immunology*
  • Pseudomonas aeruginosa Exotoxin A
  • Vibrio cholerae O1 / chemistry
  • Vibrio cholerae O1 / immunology*
  • Virulence Factors / chemistry
  • Virulence Factors / immunology*
  • Virulence Factors / pharmacology

Substances

  • Bacterial Toxins
  • Cholera Vaccines
  • Exotoxins
  • Immunoconjugates
  • Immunoglobulin M
  • Lipopolysaccharides
  • Oligosaccharides
  • Virulence Factors
  • ADP Ribose Transferases