Comparative immunogenicity of conjugates composed of Escherichia coli O111 O-specific polysaccharide, prepared by treatment with acetic acid or hydrazine, bound to tetanus toxoid by two synthetic schemes.
Escherichia coli O111, of various H types and virulence factors, causes enteritis throughout the world, especially in young children. This O type is found rarely in healthy individuals. Serum antibodies to the O-specific polysaccharide of O111 lipopolysaccharide (LPS) protect mice and dogs against infection with this E. coli serotype. The O111 O-specific polysaccharide is composed of a pentasaccharide repeat unit with two colitoses bound to the C-3 and C-6 of glucose in a trisaccharide backbone; this structure is identical to that of Salmonella adelaide (O35), another enteric pathogen. Nonpyrogenic O111 O-specific polysaccharide was prepared by treatment of its LPS with acetic acid (O-SP) or the organic base hydrazine (DeA-LPS). The O-SP had a reduced concentration of colitose. These products were derivatized with adipic acid dihydrazide (ADH) or thiolated with N-succinimidyl-3(2-pyridyldithio) propionate (SPDP). The four derivatives were covalently bound to tetanus toxoid (TT) by carbodiimide-mediated condensation or with SPDP to form conjugates. Immunization of BALB/c and general-purpose mice by a clinically acceptable route showed that DeA-LPS-TTADH, of the four conjugates, elicited the highest level of LPS antibodies. Possible reasons to explain this differential immunogenicity between the four conjugates are discussed.
Gupta
R K
RK
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Egan
W
W
Bryla
D A
DA
Robbins
J B
JB
Szu
S C
SC
D000085:Acetates / Q000737:chemistry; D019342:Acetic Acid; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry*; D001428:Bacterial Vaccines / Q000276:immunology*; D002240:Carbohydrate Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006834:Hydrazines / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019081:O Antigens; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000085:Acetates; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D006834:Hydrazines; D008070:Lipopolysaccharides; D019081:O Antigens; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; C029424:hydrazine; D019342:Acetic Acid