Development of stable Vibrio cholerae O1 Hikojima type vaccine strains co-expressing the Inaba and Ogawa lipopolysaccharide antigens.
We describe here the development of stable classical and El Tor V. cholerae O1 strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of O1 lipopolysaccharide (LPS). Mutation of the wbeT gene reduced LPS perosamine methylation and thereby gave only partial transformation into Ogawa LPS on the cell surface. The strains express approximately equal amounts of Inaba- and Ogawa-LPS antigens which are preserved after formalin-inactivation of the bacteria. Oral immunizations of both inbred and outbred mice with formalin-inactivated whole-cell vaccine preparations of these strains elicited strong intestinal IgA anti-LPS as well as serum vibriocidal antibody responses against both Inaba and Ogawa that were fully comparable to the responses induced by the licensed Dukoral vaccine. Passive protection studies in infant mice showed that immune sera raised against either of the novel Hikojima vaccine strains protected baby mice against infection with virulent strains of both serotypes. This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Stefan L
SL
Karlsson
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Elisabeth
E
Ax
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Erik
E
Nygren
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Susanne
S
Källgård
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Margareta
M
Blomquist
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Annelie
A
Ekman
Department of Medical Biochemistry and Cell Biology at Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
John
J
Benktander
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Jan
J
Holmgren
Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Michael
M
Lebens
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D022121:Cholera Vaccines / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D005798:Genes, Bacterial; D007106:Immune Sera; D007109:Immunity / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D016296:Mutagenesis / Q000235:genetics; D019081:O Antigens / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D012703:Serotyping; D015164:Vaccines, Inactivated / Q000276:immunology; D041241:Vibrio cholerae O1 / Q000145:classification / Q000235:genetics / Q000276:immunology*
D022121:Cholera Vaccines; D007106:Immune Sera; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; D019081:O Antigens; D015164:Vaccines, Inactivated