COMPARATIVE IMMUNOGENICITY OF CONJUGATES COMPOSED OF ESCHERICHIA-COLIO111 O-SPECIFIC POLYSACCHARIDE, PREPARED BY TREATMENT WITH ACETIC-ACID OR HYDRAZINE, BOUND TO TETANUS TOXOID BY 2 SYNTHETIC SCHEMES

Escherichia coli O111, of various H types and virulence factors, cause s 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 mic e and dogs against infection with this E. coli serotype. The O111 O-sp ecific polysaccharide is composed of a pentasaccharide repeat unit wit h 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 polysacc haride 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 concentr ation of colitose. These products were derivatized with adipic acid di hydrazide (ADH) or thiolated with N-succinimidyl-3(2-pyridyldithio) pr opionate (SPDP). The four derivatives were covalently bound to tetanus toroid (TT) by carbodiimide-mediated condensation or with SPDP to for m conjugates. Immunization of BALB/c and general-purpose mice by a cli nically acceptable route showed that DeA-LPST-TTADH, of the four conju gates, elicited the highest level of LPS antibodies. Possible reasons to explain this differential immunogenicity between the four conjugate s are discussed.