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Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice

DC Field Value Language
dc.contributor.author김종석-
dc.contributor.author신성재-
dc.contributor.author조상래-
dc.contributor.author차승빈-
dc.date.accessioned2016-02-04T12:02:45Z-
dc.date.available2016-02-04T12:02:45Z-
dc.date.issued2015-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/141768-
dc.description.abstractMycobacterium bovis bacillus Calmette-Guerin (BCG), the only licensed vaccine, shows limited protection efficacy against pulmonary tuberculosis (TB), particularly hypervirulent Mycobacterium tuberculosis (Mtb) strains, suggesting that a logistical and practical vaccination strategy is urgently required. Boosting the BCG-induced immunity may offer a potentially advantageous strategy for advancing TB vaccine development, instead of replacing BCG completely. Despite the improved protection of the airway immunization by using live BCG, the use of live BCG as an airway boosting agent may evoke safety concerns. Here, we analyzed the protective efficacy of γ-irradiated BCG as a BCG-prime boosting agent for airway immunization against a hypervirulent clinical strain challenge with Mycobacterium tuberculosis HN878 in a mouse TB model. After the aerosol challenge with the HN878 strain, the mice vaccinated with BCG via the parenteral route exhibited only mild and transient protection, whereas BCG vaccination followed by multiple aerosolized boosting with γ-irradiated BCG efficiently maintained long-lasting control of Mtb in terms of bacterial reduction and pathological findings. Further immunological investigation revealed that this approach resulted in a significant increase in the cellular responses in terms of a robust expansion of antigen (PPD and Ag85A)-specific CD4+ T cells concomitantly producing IFN-γ, TNF-α, and IL-2, as well as a high level of IFN-γ-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of γ-irradiated BCG is able to elicit strong Th1-biased immune responses and confer enhanced protection against a hypervirulent Mycobacterium tuberculosis HN878 infection in a boosting number-dependent manner.-
dc.description.statementOfResponsibilityopen-
dc.format.extente0141577-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAntibodies, Bacterial/blood-
dc.subject.MESHAntibodies, Bacterial/immunology-
dc.subject.MESHBCG Vaccine/administration & dosage-
dc.subject.MESHBCG Vaccine/immunology*-
dc.subject.MESHCytokines/metabolism-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHFemale-
dc.subject.MESHImmunization, Secondary*-
dc.subject.MESHImmunologic Memory-
dc.subject.MESHMice-
dc.subject.MESHMycobacterium tuberculosis/immunology*-
dc.subject.MESHMycobacterium tuberculosis/pathogenicity-
dc.subject.MESHT-Lymphocyte Subsets/immunology-
dc.subject.MESHT-Lymphocyte Subsets/metabolism-
dc.subject.MESHTuberculosis, Pulmonary/immunology*-
dc.subject.MESHTuberculosis, Pulmonary/microbiology-
dc.subject.MESHTuberculosis, Pulmonary/pathology-
dc.subject.MESHTuberculosis, Pulmonary/prevention & control-
dc.subject.MESHVaccination-
dc.subject.MESHVaccines, Inactivated*-
dc.subject.MESHVirulence-
dc.titleRepeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice-
dc.typeArticle-
dc.contributor.collegeResearcher Institutes (부설 연구소)-
dc.contributor.departmentInstitute for Immunology and Immunological Disease (면역질환연구소)-
dc.contributor.googleauthorSeung Bin Cha-
dc.contributor.googleauthorWoo Sik Kim-
dc.contributor.googleauthorJong-Seok Kim-
dc.contributor.googleauthorHongmin Kim-
dc.contributor.googleauthorKee Woong Kwon-
dc.contributor.googleauthorSeung Jung Han-
dc.contributor.googleauthorSeok-Yong Eum-
dc.contributor.googleauthorSang-Nae Cho-
dc.contributor.googleauthorSung Jae Shin-
dc.identifier.doi10.1371/journal.pone.0141577-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03824-
dc.contributor.localIdA03998-
dc.contributor.localIdA00920-
dc.contributor.localIdA02114-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid26509812-
dc.contributor.alternativeNameKim, Jong Seok-
dc.contributor.alternativeNameShin, Sung Jae-
dc.contributor.alternativeNameCho, Sang Nae-
dc.contributor.alternativeNameCha, Seung Bin-
dc.contributor.affiliatedAuthorCho, Sang Nae-
dc.contributor.affiliatedAuthorCha, Seung Bin-
dc.contributor.affiliatedAuthorKim, Jong Seok-
dc.contributor.affiliatedAuthorShin, Sung Jae-
dc.rights.accessRightsfree-
dc.citation.volume10-
dc.citation.number10-
dc.citation.startPagee0141577-
dc.identifier.bibliographicCitationPLOS ONE, Vol.10(10) : e0141577, 2015-
dc.identifier.rimsid30875-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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