Development of Shigella sonnei live oral vaccines based on defined rfbInaba deletion mutants of Vibrio cholerae expressing the Shigella serotype D O polysaccharide.
Previous experimentation has highlighted a number of difficulties in the development of carrier-based bivalent vaccines (J.-F. Viret and D. Favre, Biologicals 22:361-372, 1994) In an attempt to obviate these carrier strains. Toward this aim, a series of defined rfbInaba deletion (delta rfbInaba) mutants of the cholera vaccine strain V. cholerae CVD103-HgR (O1 Inaba serotype) and derivative bearing the chromosomally integrated locus encoding the S. sonnei O-PS were constructed and characterized. The various mutations disrupt genes thought to be involved in either the synthesis of perosamine, the synthesis of 3-deoxy-L-glycero tetronic acid, or the O-PS transport functions together with synthesis of the perosamine synthetase. Some deletions were obtained only in strains expressing the heterologous lipopolysaccharide (LPS). Viable delta rfbInaba deletions in CVD103-HgR profoundly altered some of its phenotypic properties. The same deletions present in CVD103-HgR derivatives expressing the heterologous LPS affected their phenotypes only to a lesser extent. Only in strains in which perosamine synthesis was specifically abolished could high amounts of core-bound S. sonnei O-PS be synthesized. Two such strains (CH21, which expresses both the R1 core and the S. sonnei O-PS, and CH22, which expresses only the latter antigenic determinant) were further analyzed and were found to be indistinguishable from CVD103-HgR with regard to lack of enterotoxin activity, choleragenoid production, mercury resistance, pilin production, and, for CH22, motility. Mice immunized with CH22 produced high titers of S. sonnei O-PS-specific antibodies.
Favre
D
D
Swiss Serum and Vaccine Institute, Bern, Switzerland.
Cryz
S J
SJ
Viret
J F
JF
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D003001:Cloning, Molecular; D017353:Gene Deletion; D005822:Genetic Vectors; D007114:Immunization; D051379:Mice; D019081:O Antigens / Q000096:biosynthesis*; D012764:Shigella sonnei / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014734:Vibrio cholerae / Q000235:genetics*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D019081:O Antigens; D014614:Vaccines, Synthetic