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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

Survival rates and bacterial loads in organs of intranasally immunized BALB/c mice after intranasal challenge with B. thailandensis (5 x 106 CFU).(A) Mice were immunized with PBS, SL3261 (vector), or SL3261/p1C3 (vaccine) via the intranasal route, then challenged. Mice were monitored for survival for a period up 150 h post-challenge. Results are represented in Kaplan-Meier survival curves and were analyzed by log-rank test. Log-rank: PBS vs. vaccine (P = 0.0031); vector vs. vaccine (P = 0.0128). Median survival: PBS, 64 h; SL3261, 84 h; and SL3261/p1C3, undefined). Results are representative of three independent experiments, five mice each. (B, C) Bacterial load in the organs of intranasally immunized mice 72 h post-challenge. All samples were plated for viable CFU on TSA and Ashdown’s agar. Each point represents a single mouse. ND indicates not detected. Data was analyzed by the Mann-Whitney U test. Nasal wash (P = 0.0012 vaccine vs. vector and P = 0.0025 vaccine vs. PBS); lung (P = 0.0043 vector vs. PBS); liver (P = 0.0043 vector vs. PBS).
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pone.0132032.g004: Survival rates and bacterial loads in organs of intranasally immunized BALB/c mice after intranasal challenge with B. thailandensis (5 x 106 CFU).(A) Mice were immunized with PBS, SL3261 (vector), or SL3261/p1C3 (vaccine) via the intranasal route, then challenged. Mice were monitored for survival for a period up 150 h post-challenge. Results are represented in Kaplan-Meier survival curves and were analyzed by log-rank test. Log-rank: PBS vs. vaccine (P = 0.0031); vector vs. vaccine (P = 0.0128). Median survival: PBS, 64 h; SL3261, 84 h; and SL3261/p1C3, undefined). Results are representative of three independent experiments, five mice each. (B, C) Bacterial load in the organs of intranasally immunized mice 72 h post-challenge. All samples were plated for viable CFU on TSA and Ashdown’s agar. Each point represents a single mouse. ND indicates not detected. Data was analyzed by the Mann-Whitney U test. Nasal wash (P = 0.0012 vaccine vs. vector and P = 0.0025 vaccine vs. PBS); lung (P = 0.0043 vector vs. PBS); liver (P = 0.0043 vector vs. PBS).

Mentions: To investigate the ability of the SL3261/p1C3 to confer protection, vaccinated animals were intranasally challenged with a lethal dose of B. thailandensis (5 x 106 CFU). No morbidity was observed in vaccine-immunized mice. On the other hand, all PBS-treated mice were dead at 100 h post-infection and 60% of vector-immunized mice were dead at 125 h post-infection (Fig 4A).


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)

Survival rates and bacterial loads in organs of intranasally immunized BALB/c mice after intranasal challenge with B. thailandensis (5 x 106 CFU).(A) Mice were immunized with PBS, SL3261 (vector), or SL3261/p1C3 (vaccine) via the intranasal route, then challenged. Mice were monitored for survival for a period up 150 h post-challenge. Results are represented in Kaplan-Meier survival curves and were analyzed by log-rank test. Log-rank: PBS vs. vaccine (P = 0.0031); vector vs. vaccine (P = 0.0128). Median survival: PBS, 64 h; SL3261, 84 h; and SL3261/p1C3, undefined). Results are representative of three independent experiments, five mice each. (B, C) Bacterial load in the organs of intranasally immunized mice 72 h post-challenge. All samples were plated for viable CFU on TSA and Ashdown’s agar. Each point represents a single mouse. ND indicates not detected. Data was analyzed by the Mann-Whitney U test. Nasal wash (P = 0.0012 vaccine vs. vector and P = 0.0025 vaccine vs. PBS); lung (P = 0.0043 vector vs. PBS); liver (P = 0.0043 vector vs. PBS).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4492786&req=5

pone.0132032.g004: Survival rates and bacterial loads in organs of intranasally immunized BALB/c mice after intranasal challenge with B. thailandensis (5 x 106 CFU).(A) Mice were immunized with PBS, SL3261 (vector), or SL3261/p1C3 (vaccine) via the intranasal route, then challenged. Mice were monitored for survival for a period up 150 h post-challenge. Results are represented in Kaplan-Meier survival curves and were analyzed by log-rank test. Log-rank: PBS vs. vaccine (P = 0.0031); vector vs. vaccine (P = 0.0128). Median survival: PBS, 64 h; SL3261, 84 h; and SL3261/p1C3, undefined). Results are representative of three independent experiments, five mice each. (B, C) Bacterial load in the organs of intranasally immunized mice 72 h post-challenge. All samples were plated for viable CFU on TSA and Ashdown’s agar. Each point represents a single mouse. ND indicates not detected. Data was analyzed by the Mann-Whitney U test. Nasal wash (P = 0.0012 vaccine vs. vector and P = 0.0025 vaccine vs. PBS); lung (P = 0.0043 vector vs. PBS); liver (P = 0.0043 vector vs. PBS).
Mentions: To investigate the ability of the SL3261/p1C3 to confer protection, vaccinated animals were intranasally challenged with a lethal dose of B. thailandensis (5 x 106 CFU). No morbidity was observed in vaccine-immunized mice. On the other hand, all PBS-treated mice were dead at 100 h post-infection and 60% of vector-immunized mice were dead at 125 h post-infection (Fig 4A).

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