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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 cytokine 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. P values were calculated as: Vaccine vs. PBS and Vector vs. PBS.
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pone.0132032.g003: Serum cytokine 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. P values were calculated as: Vaccine vs. PBS and Vector vs. PBS.

Mentions: The cytokine/chemokine responses of the PBS, vector-, and vaccine-immunized mice at 4 weeks post-initial immunization were determined by quantification of a panel of Th1/Th2 cytokines in pooled sera using a mouse cytokine magnetic 20-Plex Panel. Significantly higher levels of IFN-γ, IL-12p70, IL-5, TNF-α, and IL-10 were detected in the pooled sera of vaccine and vector immunized animals when compared to the respective PBS immunized mice. Also greater serum concentrations of IL-2, IL-4, IL-6, and GM-CSF were observed in vaccine- and vector-immunized mice (Fig 3).


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 cytokine 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. P values were calculated as: Vaccine vs. PBS and Vector vs. PBS.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132032.g003: Serum cytokine 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. P values were calculated as: Vaccine vs. PBS and Vector vs. PBS.
Mentions: The cytokine/chemokine responses of the PBS, vector-, and vaccine-immunized mice at 4 weeks post-initial immunization were determined by quantification of a panel of Th1/Th2 cytokines in pooled sera using a mouse cytokine magnetic 20-Plex Panel. Significantly higher levels of IFN-γ, IL-12p70, IL-5, TNF-α, and IL-10 were detected in the pooled sera of vaccine and vector immunized animals when compared to the respective PBS immunized mice. Also greater serum concentrations of IL-2, IL-4, IL-6, and GM-CSF were observed in vaccine- and vector-immunized mice (Fig 3).

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