Artificial Salmonella Vaccines: Salmonella typhimurium O-Antigen-Specific Oligosaccharide-Protein Conjugates Elicit Protective Antibodies in Rabbits and Mice

Publisher Website
Google Scholar
Abstract
Several saccharides representative of the O-antigenic polysaccharide chain of S. typhimurium (O antigens 4 and 12) were used as haptenic groups covalently linked to bovine serum albumin. The disaccharide abequose 1 .fwdarw. 3 D-mannose was synthesized and the .**GRAPHIC**. tetra-, octa- and dodecasaccharides were isolated after cleavage of isolated S. typhimurium O-polysaccharide chains by using bacteriophage endo-glycosidases. Rabbits immunized with the saccharide-protein conjugates suspended in Freund complete adjuvant readily responded with O4 antibody titers as high, or almost as high, as those elicited by heat-killed bacteria. The octa- and dodecasaccharide conjugates also gave rise to O12 antibody titers. The antibody response in mice differed in 2 ways from that seen in rabbits: mice did not respond with measurable antibody production against the disaccharide haptens and the highest S. typhimurium lipopolysaccharide antibody response elicited by the saccharide haptens was still .apprx. 50-fold lower than that elicited by heat-killed bacteria. The latter difference may be a consequence of the fact that the mouse preferentially produces antibodies against the galactose residue which is terminal in the hapten but not in the native O-antigenic polysaccharide chain. Antibodies elicited in rabbits against all saccharide-protein conjugates protected passively transferred mice against i.p. challenge with 100 LD50 of S. typhimurium SH 2201 (O4, 12) but not against challenge with S. enteritidis SH 2204 (O9, 12). The antibodies elicited by the saccharide-protein conjugates protected as well as antibodies elicited by heat-killed bacteria.