Preparation, characterization, and immunogenicity of conjugates composed of the O-specific polysaccharide of Shigella dysenteriae type 1 (Shiga's bacillus) bound to tetanus toxoid.
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.
Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
C Y
CY
Chu
B K
BK
Liu
D
D
Watson
S S
SS
Szu
D
D
Bryla
J
J
Shiloach
R
R
Schneerson
J B
JB
Robbins
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001428:Bacterial Vaccines / Q000276:immunology*; D003429:Cross Reactions; D007106:Immune Sera / Q000276:immunology; D008070:Lipopolysaccharides / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000032:analysis / Q000276:immunology*; D012762:Shigella dysenteriae / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007106:Immune Sera; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic