Preparation, characterization, and immunogenicity of conjugates composed of the O-specific polysaccharide of Shigella dysenteriae type 1 (Shiga's bacillus) bound to tetanus toxoid

Infect Immun. 1991 Dec;59(12):4450-8. doi: 10.1128/iai.59.12.4450-4458.1991.

Abstract

The background for developing conjugate vaccines for shigellosis composed of the O-specific polysaccharide (O-SP) bound to a protein is described elsewhere (C. Y. Chu, R. Schneerson, and J. B. Robbins, submitted for publication). Briefly, there is direct evidence for type (lipopolysaccharide [LPS])-specific protection after infection with the wild type or with attenuated strains of shigellae. Prospective studies of Israeli armed forces recruits show a correlation between preexisting serum immunoglobulin G (IgG) LPS antibodies and resistance to shigellosis (D. Cohen, M. S. Green, C. Block, R. Slephon, and I. Ofek, J. Clin. Microbiol. 29:386-389, 1991). In order to elicit IgG LPS-specific antibodies to Shigella dysenteriae type 1, the O-SP of this pathogen was purified and bound to tetanus toxoid (TT) by three schemes. The most immunogenic used a modification of a published method (C. Y. Chu, R. Schneerson, J. B. Robbins, and S. C. Rastogi, Infect. Immun. 40:245-256, 1983). The resultant O-SP-TT conjugates were stable and elicited high levels of IgG O-SP antibodies and booster responses in young mice when injected subcutaneously in saline at 1/10 the proposed human dose. Adsorption onto alum or concurrent administration with monophosphoryl lipid A enhanced both the IgG and IgM antibody responses to the O-SP of the conjugate; both the nonadsorbed and adsorbed conjugates elicited higher rises of IgG than of IgM antibodies. Clinical evaluations of S. dysenteriae type 1 O-SP-TT conjugates are planned.

MeSH terms

  • Animals
  • Antibodies, Bacterial / analysis
  • Bacterial Vaccines / immunology*
  • Cross Reactions
  • Immune Sera / immunology
  • Lipopolysaccharides / analysis
  • Magnetic Resonance Spectroscopy
  • Mice
  • Polysaccharides, Bacterial / analysis
  • Polysaccharides, Bacterial / immunology*
  • Shigella dysenteriae / immunology*
  • Shigella flexneri / immunology
  • Tetanus Toxoid / immunology*
  • Vaccines, Synthetic / immunology*

Substances

  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Immune Sera
  • Lipopolysaccharides
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • Vaccines, Synthetic