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...

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Published in:	PloS one 2014, Vol.9 (11), p.e108521-e108521
Main Authors:	Karlsson, Stefan L, Ax, Elisabeth, Nygren, Erik, Källgård, Susanne, Blomquist, Margareta, Ekman, Annelie, Benktander, John, Holmgren, Jan, Lebens, Michael
Format:	Article
Language:	eng
Subjects:	1992 1994 adult animal animal experiment animal model animal tissue Animals antibody blood level Antibody Formation Antibody Formation - immunology antibody production antibody response antibody specificity antibody titer Antigens Antisera antiserum B-SUBUNIT BACTERIA Bacterial bacterial antigen bacterial gene BACTERIAL PATHOGENESIS bacterial strain bacterium lipopolysaccharide Biology and Life Sciences Cell surface CHAIN Cholera cholera vaccine Cholera Vaccines Cholera Vaccines - immunology classification Clinical Medicine COLONIZATION FACTORS CONSTRUCTION controlled study cross reaction Cross Reactions Cross Reactions - immunology Deactivation DNA methylation E coli EFFICACY Enzymes ESCHERICHIA-COLI ETEC female Formaldehyde gene mutation Genes Genes, Bacterial genetic manipulation genetic stability Genetic transformation genetics Immune Sera Immune serum immunity Immunity - immunology immunogenicity Immunoglobulin A Immunoglobulin A - immunology immunoglobulin A antibody immunoglobulin M antibody Immunology Inaba antigen Inactivated inactivated vaccine Inactivation Inbreeding infant infection prevention Infections Intestinal Mucosa Intestinal Mucosa - immunology Intestine intestine mucosa Klinisk medicin lipopolysaccharide Lipopolysaccharides Lipopolysaccharides - metabolism LORENZO V Medicine and Health Sciences metabolism MICE MONOCLONAL-ANTIBODIES mouse Multidisciplinary Sciences Mutagenesis Mutagenesis - genetics Mutation nonhuman O antigen O Antigens O Antigens - metabolism Ogawa antigen P386 Pathogens plasmid Plasmids Plasmids - metabolism PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES PT A ROEHER UH Serotypes Serotyping site directed mutagenesis Strains (organisms) Survival analysis survival rate Transformation unclassified drug V235 Vaccines Vaccines, Inactivated - immunology Vibrio cholerae Vibrio cholerae O1 Vibrio cholerae O1 - classification Vibrio cholerae O1 - genetics Vibrio cholerae O1 - immunology Waterborne diseases WbeT gene
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Summary:	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.
ISSN:	1932-6203 1932-6203