title: Aerogenic vaccination with a Burkholderia mallei auxotroph protects against aerosol-initiated glanders in mice.
abstract: Burkholderia mallei is an obligate mammalian pathogen that causes the zoonotic disease glanders. Two live attenuated B. mallei strains, a capsule mutant and a branched-chain amino acid auxotroph, were evaluated for use as vaccines against aerosol-initiated glanders in mice. Animals were aerogenically vaccinated and serum samples were obtained before aerosol challenge with a high-dose (>300 times the LD50) of B. mallei ATCC 23344. Mice vaccinated with the capsule mutant developed a Th2-like Ig subclass antibody response and none survived beyond 5 days. In comparison, the auxotrophic mutant elicited a Th1-like Ig subclass antibody response and 25% of the animals survived for 1 month postchallenge. After a low-dose (5 times the LD50) aerosol challenge, the survival rates of auxotroph-vaccinated and unvaccinated animals were 50 and 0%, respectively. Thus, live attenuated strains that promote a Th1-like Ig response may serve as promising vaccine candidates against aerosol infection with B. mallei.
authors.affiliation: Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702, USA.
authors.forename: Ricky L
authors.initials: RL
authors.lastname: Ulrich
authors.forename: Kei
authors.initials: K
authors.lastname: Amemiya
authors.forename: David M
authors.initials: DM
authors.lastname: Waag
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.forename: David
authors.initials: D
authors.lastname: DeShazer
mesh_terms: D000336:Aerosols; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D042726:Burkholderia mallei / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D005896:Glanders / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000336:Aerosols; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004269:DNA, Bacterial; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated