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Development of stable Vibrio cholerae O1 Hikojima type vaccine strains co-expressing the Inaba and Ogawa lipopolysaccharide antigens.

Karlsson SL, Ax E, Nygren E, Källgård S, Blomquist M, Ekman A, Benktander J, Holmgren J, Lebens M - PLoS ONE (2014)

Bottom Line: 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.This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
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.

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Related in: MedlinePlus

Comparison of intestinal–mucosal IgA anti–LPS and serum vibriocidal antibody responses elicited by oral immunization with formalin–killed MS1568 or Dukoral vaccines in CD1 mice.(A) IgA anti–LPS antibody levels measured by ELISA in fecal extracts (dashed) and in small intestinal tissue extracts (striped) after two rounds of intragastric immunizations and (B) same after three rounds as described in Material and Methods. (C) Serum vibriocidal antibody responses against Inaba (filled) and Ogawa (open) test organisms after two and (D) three rounds of immunizations. Bars show geometric mean values and SEM for 7 animals per group. As tested with ANOVA, post–immunization antibody levels did not differ significantly between any of the different immunization groups.
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pone-0108521-g005: Comparison of intestinal–mucosal IgA anti–LPS and serum vibriocidal antibody responses elicited by oral immunization with formalin–killed MS1568 or Dukoral vaccines in CD1 mice.(A) IgA anti–LPS antibody levels measured by ELISA in fecal extracts (dashed) and in small intestinal tissue extracts (striped) after two rounds of intragastric immunizations and (B) same after three rounds as described in Material and Methods. (C) Serum vibriocidal antibody responses against Inaba (filled) and Ogawa (open) test organisms after two and (D) three rounds of immunizations. Bars show geometric mean values and SEM for 7 animals per group. As tested with ANOVA, post–immunization antibody levels did not differ significantly between any of the different immunization groups.

Mentions: Closely similar fecal and intestinal IgA anti–LPS responses were obtained in outbred CD1 mice immunized orally/intragastrically by either two or three rounds with formalin–killed MS1568 vaccine as compared with Dukoral. The fecal and intestinal tissue extract IgA anti–LPS responses to the MS1568 vaccine were fully comparable to those against the Dukoral vaccine after either two or three rounds of immunization, which latter resulted in ca 2– to 20–fold further increased locally produced IgA levels compared to those after two immunization rounds (Figure 5A and B).


Development of stable Vibrio cholerae O1 Hikojima type vaccine strains co-expressing the Inaba and Ogawa lipopolysaccharide antigens.

Karlsson SL, Ax E, Nygren E, Källgård S, Blomquist M, Ekman A, Benktander J, Holmgren J, Lebens M - PLoS ONE (2014)

Comparison of intestinal–mucosal IgA anti–LPS and serum vibriocidal antibody responses elicited by oral immunization with formalin–killed MS1568 or Dukoral vaccines in CD1 mice.(A) IgA anti–LPS antibody levels measured by ELISA in fecal extracts (dashed) and in small intestinal tissue extracts (striped) after two rounds of intragastric immunizations and (B) same after three rounds as described in Material and Methods. (C) Serum vibriocidal antibody responses against Inaba (filled) and Ogawa (open) test organisms after two and (D) three rounds of immunizations. Bars show geometric mean values and SEM for 7 animals per group. As tested with ANOVA, post–immunization antibody levels did not differ significantly between any of the different immunization groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232259&req=5

pone-0108521-g005: Comparison of intestinal–mucosal IgA anti–LPS and serum vibriocidal antibody responses elicited by oral immunization with formalin–killed MS1568 or Dukoral vaccines in CD1 mice.(A) IgA anti–LPS antibody levels measured by ELISA in fecal extracts (dashed) and in small intestinal tissue extracts (striped) after two rounds of intragastric immunizations and (B) same after three rounds as described in Material and Methods. (C) Serum vibriocidal antibody responses against Inaba (filled) and Ogawa (open) test organisms after two and (D) three rounds of immunizations. Bars show geometric mean values and SEM for 7 animals per group. As tested with ANOVA, post–immunization antibody levels did not differ significantly between any of the different immunization groups.
Mentions: Closely similar fecal and intestinal IgA anti–LPS responses were obtained in outbred CD1 mice immunized orally/intragastrically by either two or three rounds with formalin–killed MS1568 vaccine as compared with Dukoral. The fecal and intestinal tissue extract IgA anti–LPS responses to the MS1568 vaccine were fully comparable to those against the Dukoral vaccine after either two or three rounds of immunization, which latter resulted in ca 2– to 20–fold further increased locally produced IgA levels compared to those after two immunization rounds (Figure 5A and B).

Bottom Line: 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.This study illustrates the power of using genetic manipulation to improve the properties of bacteria strains for use in killed whole-cell vaccines.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus