title: Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders.
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.
authors.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.
authors.forename: Dina A
authors.initials: DA
authors.lastname: Moustafa
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Scarff
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Preston P
authors.initials: PP
authors.lastname: Garcia
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Sara K B
authors.initials: SK
authors.lastname: Cassidy
authors.affiliation: Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America; Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: DiGiandomenico
authors.affiliation: Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Waag
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine and Virginia Tech-Carilion School of Medicine, Virginia Tech, Blacksburg, Virginia, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Inzana
authors.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.
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D042726:Burkholderia mallei / Q000235:genetics* / Q000276:immunology; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression; D005896:Glanders / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D008554:Melioidosis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D019081:O Antigens / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*
chemical_list: D001428:Bacterial Vaccines; D019081:O Antigens