Repeated aerosolized-boosting with gamma-irradiated mycobacterium bovis BCG confers improved pulmonary protection against the hypervirulent mycobacterium tuberculosis strain HN878 in Mice

Seung Bin Cha, Woo Sik Kim, Jong Seok Kim, Hongmin Kim, Kee Woong Kwon, Seung Jung Han, Seok Yong Eum, Sangnae Cho, SungJae Shin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mycobacterium 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 ?-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 ?- 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-a, and IL-2, as well as a high level of IFN-?-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of ?-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.

Original languageEnglish
Article number0141577
JournalPLoS One
Volume10
Issue number10
DOIs
Publication statusPublished - 2015 Oct 28

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Mycobacterium bovis BCG
Mycobacterium bovis
Mycobacterium tuberculosis
Bacilli
lungs
Lung
mice
tuberculosis
Immunization
immunization
Vaccination
vaccination
Tuberculosis Vaccines
T-cells
Immune system
Tuberculin
vaccine development
aerosols
interleukin-2
Aerosols

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "Repeated aerosolized-boosting with gamma-irradiated mycobacterium bovis BCG confers improved pulmonary protection against the hypervirulent mycobacterium tuberculosis strain HN878 in Mice",
abstract = "Mycobacterium 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 ?-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 ?- 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-a, and IL-2, as well as a high level of IFN-?-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of ?-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.",
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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. / Cha, Seung Bin; Kim, Woo Sik; Kim, Jong Seok; Kim, Hongmin; Kwon, Kee Woong; Han, Seung Jung; Eum, Seok Yong; Cho, Sangnae; Shin, SungJae.

In: PLoS One, Vol. 10, No. 10, 0141577, 28.10.2015.

Research output: Contribution to journalArticle

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AU - Cha, Seung Bin

AU - Kim, Woo Sik

AU - Kim, Jong Seok

AU - Kim, Hongmin

AU - Kwon, Kee Woong

AU - Han, Seung Jung

AU - Eum, Seok Yong

AU - Cho, Sangnae

AU - Shin, SungJae

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AB - Mycobacterium 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 ?-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 ?- 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-a, and IL-2, as well as a high level of IFN-?-producing recall response via both the local and systemic immune systems upon further boosting. Collectively, aerosolized boosting of ?-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.

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