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Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders.

Moustafa DA, Scarff JM, Garcia PP, Cassidy SK, DiGiandomenico A, Waag DM, Inzana TJ, Goldberg JB - PLoS ONE (2015)

Bottom Line: Consequently efforts are directed towards the development of an efficacious and safe vaccine.Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses.These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America; Department of Pediatrics, Emory University School of Medicine and Children's Hospital of Atlanta, Inc., Atlanta, Georgia, United States of America.

ABSTRACT
Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

No MeSH data available.


Related in: MedlinePlus

Serum antibody response of BALB/c mice following intranasal immunization with S. enterica serovar Typhimurium SL3261 expressing B. mallei O antigen.Sera were collected 4 weeks post-vaccination, and the data were analyzed by the Mann-Whitney U test. Serum IgG and IgM response to: (A)B. mallei LPS (P < 0.0001 vector vs. vaccine for IgG and IgM); (B)B. pseudomallei LPS (P < 0.0003 vector vs. vaccine for IgG, and P < 0.0079 for IgM); (C)B. thailandensis E264 lysate (P < 0.005 PBS vs. vaccine, and P < 0.0005 vector vs. vaccine). (D) Specific IgG response in the sera of intranasally-immunized BALB/c mice to B. mallei LPS or anti-B. thailandensis.
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pone.0132032.g002: Serum antibody response of BALB/c mice following intranasal immunization with S. enterica serovar Typhimurium SL3261 expressing B. mallei O antigen.Sera were collected 4 weeks post-vaccination, and the data were analyzed by the Mann-Whitney U test. Serum IgG and IgM response to: (A)B. mallei LPS (P < 0.0001 vector vs. vaccine for IgG and IgM); (B)B. pseudomallei LPS (P < 0.0003 vector vs. vaccine for IgG, and P < 0.0079 for IgM); (C)B. thailandensis E264 lysate (P < 0.005 PBS vs. vaccine, and P < 0.0005 vector vs. vaccine). (D) Specific IgG response in the sera of intranasally-immunized BALB/c mice to B. mallei LPS or anti-B. thailandensis.

Mentions: ELISA analysis using sera collected four weeks post-immunization from BALB/c mice that received the vaccine revealed robust B. mallei LPS-specific IgG and IgM antibody response when compared with sera from the vector-immunized or PBS control mice (Fig 2A). Moreover, sera from intranasally vaccinated animals were also reactive to B. pseudomallei LPS (Fig 2B). We next examined the IgG and IgM antibodies specific to B. thailandensis. Sera from vaccine-immunized BALB/c mice after intranasal immunization showed significant levels of anti-B. thailandensis IgG compared to the control groups. B. thailandensis-specific IgM levels in the vaccine group were not significantly greater when compared to those of the vector-immunized groups (Fig 2C).


Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders.

Moustafa DA, Scarff JM, Garcia PP, Cassidy SK, DiGiandomenico A, Waag DM, Inzana TJ, Goldberg JB - PLoS ONE (2015)

Serum antibody response of BALB/c mice following intranasal immunization with S. enterica serovar Typhimurium SL3261 expressing B. mallei O antigen.Sera were collected 4 weeks post-vaccination, and the data were analyzed by the Mann-Whitney U test. Serum IgG and IgM response to: (A)B. mallei LPS (P < 0.0001 vector vs. vaccine for IgG and IgM); (B)B. pseudomallei LPS (P < 0.0003 vector vs. vaccine for IgG, and P < 0.0079 for IgM); (C)B. thailandensis E264 lysate (P < 0.005 PBS vs. vaccine, and P < 0.0005 vector vs. vaccine). (D) Specific IgG response in the sera of intranasally-immunized BALB/c mice to B. mallei LPS or anti-B. thailandensis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492786&req=5

pone.0132032.g002: Serum antibody response of BALB/c mice following intranasal immunization with S. enterica serovar Typhimurium SL3261 expressing B. mallei O antigen.Sera were collected 4 weeks post-vaccination, and the data were analyzed by the Mann-Whitney U test. Serum IgG and IgM response to: (A)B. mallei LPS (P < 0.0001 vector vs. vaccine for IgG and IgM); (B)B. pseudomallei LPS (P < 0.0003 vector vs. vaccine for IgG, and P < 0.0079 for IgM); (C)B. thailandensis E264 lysate (P < 0.005 PBS vs. vaccine, and P < 0.0005 vector vs. vaccine). (D) Specific IgG response in the sera of intranasally-immunized BALB/c mice to B. mallei LPS or anti-B. thailandensis.
Mentions: ELISA analysis using sera collected four weeks post-immunization from BALB/c mice that received the vaccine revealed robust B. mallei LPS-specific IgG and IgM antibody response when compared with sera from the vector-immunized or PBS control mice (Fig 2A). Moreover, sera from intranasally vaccinated animals were also reactive to B. pseudomallei LPS (Fig 2B). We next examined the IgG and IgM antibodies specific to B. thailandensis. Sera from vaccine-immunized BALB/c mice after intranasal immunization showed significant levels of anti-B. thailandensis IgG compared to the control groups. B. thailandensis-specific IgM levels in the vaccine group were not significantly greater when compared to those of the vector-immunized groups (Fig 2C).

Bottom Line: Consequently efforts are directed towards the development of an efficacious and safe vaccine.Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses.These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America; Department of Pediatrics, Emory University School of Medicine and Children's Hospital of Atlanta, Inc., Atlanta, Georgia, United States of America.

ABSTRACT
Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

No MeSH data available.


Related in: MedlinePlus