Intranasal immunization with DnaK protein induces protective mucosal immunity against tuberculosis in CD4-depleted mice

Yu Min Chuang, Michael L. Pinn, Petros Karakousis, Chien-Fu Hung

Research output: Contribution to journalArticle

Abstract

Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Guérin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFNγ-secreting CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination can generate protection against Mtb similar to BCG, underscoring its potential utility as an Mtb vaccine candidate in humans.

Original languageEnglish (US)
Article number31
JournalFrontiers in cellular and infection microbiology
Volume8
Issue numberFEB
DOIs
StatePublished - Feb 8 2018

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Mucosal Immunity
Immunization
Vaccination
Tuberculosis
Mycobacterium tuberculosis
Bacillus
Tuberculosis Vaccines
Proteins
T-Lymphocytes
Immunity
Vaccines
BCG Vaccine
Lung
Mycobacterium Infections
DNA Vaccines
Interleukin-17
Inbred C57BL Mouse
Spleen

Keywords

  • DnaK
  • Immunodeficiency
  • Intranasal
  • Tuberculosis
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

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title = "Intranasal immunization with DnaK protein induces protective mucosal immunity against tuberculosis in CD4-depleted mice",
abstract = "Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Gu{\'e}rin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFNγ-secreting CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination can generate protection against Mtb similar to BCG, underscoring its potential utility as an Mtb vaccine candidate in humans.",
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N2 - Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Guérin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFNγ-secreting CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination can generate protection against Mtb similar to BCG, underscoring its potential utility as an Mtb vaccine candidate in humans.

AB - Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Guérin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFNγ-secreting CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination can generate protection against Mtb similar to BCG, underscoring its potential utility as an Mtb vaccine candidate in humans.

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