title: Combining vaccination and postexposure CpG therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis.
abstract: The Gram-negative bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a major cause of lethal sepsis and morbidity in endemic areas of Southeast Asia and a potential bioterrorism threat. We have used susceptible BALB/c mice to evaluate the potential of targeting vaccination and generic immunotherapy to the lung for optimal protection against respiratory challenge. Intranasal vaccination with live attenuated B. pseudomallei increased survival and induced interferon-γ-secreting T cells in the lung. Intranasal delivery of CpG oligodeoxynucleotides also provided significant protection; however, combining preexposure vaccination with CpG treatment at the time of infection or up to 18 hours after infection, provided significantly greater protection than either treatment alone. This combination prolonged survival, decreased bacterial loads by >1000-fold, and delayed the onset of sepsis. This novel approach may be applicable to other potential biodefense agents for which existing countermeasures are not fully effective.
authors.affiliation: Centre for Clinical Microbiology, Royal Free Campus University College London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Easton
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.forename: Karen
authors.initials: K
authors.lastname: Chu
authors.forename: Natasha
authors.initials: N
authors.lastname: Patel
authors.forename: Roman A
authors.initials: RA
authors.lastname: Lukaszewski
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Krieg
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D054045:Biological Warfare Agents; D016957:Burkholderia pseudomallei; D018899:CpG Islands / Q000276:immunology; D005260:Female; D008168:Lung / Q000382:microbiology; D008554:Melioidosis / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D054045:Biological Warfare Agents; C523579:CPG 10101; C527702:CpG ODN 2395; D009838:Oligodeoxyribonucleotides