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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

Opsonophagocytosis killing of B. thailandensis.In vitro opsonophagocytic killing of B. thailandensis E264lux using dilutions of pooled antisera collected from intranasally PBS-, SL3261 (vector)-, and SL3261/p1C3 (vaccine)-immunized BALB/c mice. Plates were read at 120 min following the co-incubation of the opsonophagocytosis assay components. Bars represent mean percentage of killing, and error bars represent the standard deviation. Data were analyzed by the Mann-Whitney U test (P<0.0005 vaccine vs. no sera; P<0.005 vaccine vs. vector).
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pone.0132032.g006: Opsonophagocytosis killing of B. thailandensis.In vitro opsonophagocytic killing of B. thailandensis E264lux using dilutions of pooled antisera collected from intranasally PBS-, SL3261 (vector)-, and SL3261/p1C3 (vaccine)-immunized BALB/c mice. Plates were read at 120 min following the co-incubation of the opsonophagocytosis assay components. Bars represent mean percentage of killing, and error bars represent the standard deviation. Data were analyzed by the Mann-Whitney U test (P<0.0005 vaccine vs. no sera; P<0.005 vaccine vs. vector).

Mentions: We examined the efficiency immune sera to promote opsonization and phagocytosis of B. thailandensis by PMN. As a control, we performed the assay in absence of vaccine-immune sera to further confirm the role of antibodies in the protection. Pooled antisera from vaccine-immunized mice mediated biologically significant level of opsonophagocytic killing (>50%) of B. thailandensis strains at serum dilutions up to 1:72,900 compared to limited killing observed with pooled sera from vector-immunized mice (1:2,700). Furthermore, no killing of strain E264lux was observed in absence of vaccine immune sera (Fig 6). These results suggest that one of the mechanisms for the observed protection is opsonophagocytosis of B. thailandensis.


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)

Opsonophagocytosis killing of B. thailandensis.In vitro opsonophagocytic killing of B. thailandensis E264lux using dilutions of pooled antisera collected from intranasally PBS-, SL3261 (vector)-, and SL3261/p1C3 (vaccine)-immunized BALB/c mice. Plates were read at 120 min following the co-incubation of the opsonophagocytosis assay components. Bars represent mean percentage of killing, and error bars represent the standard deviation. Data were analyzed by the Mann-Whitney U test (P<0.0005 vaccine vs. no sera; P<0.005 vaccine vs. vector).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132032.g006: Opsonophagocytosis killing of B. thailandensis.In vitro opsonophagocytic killing of B. thailandensis E264lux using dilutions of pooled antisera collected from intranasally PBS-, SL3261 (vector)-, and SL3261/p1C3 (vaccine)-immunized BALB/c mice. Plates were read at 120 min following the co-incubation of the opsonophagocytosis assay components. Bars represent mean percentage of killing, and error bars represent the standard deviation. Data were analyzed by the Mann-Whitney U test (P<0.0005 vaccine vs. no sera; P<0.005 vaccine vs. vector).
Mentions: We examined the efficiency immune sera to promote opsonization and phagocytosis of B. thailandensis by PMN. As a control, we performed the assay in absence of vaccine-immune sera to further confirm the role of antibodies in the protection. Pooled antisera from vaccine-immunized mice mediated biologically significant level of opsonophagocytic killing (>50%) of B. thailandensis strains at serum dilutions up to 1:72,900 compared to limited killing observed with pooled sera from vector-immunized mice (1:2,700). Furthermore, no killing of strain E264lux was observed in absence of vaccine immune sera (Fig 6). These results suggest that one of the mechanisms for the observed protection is opsonophagocytosis of B. thailandensis.

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