Protective vaccine efficacy of the complete form of PPE39 protein from mycobacterium tuberculosis Beijing/K strain in mice

Ahreum Kim, Yun Gyoung Hur, Sunwha Gu, Sangnae Cho

Research output: Contribution to journalArticle

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Abstract

The aim of this study was to evaluate the protective efficacy of MTBK_ 24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (P 0.05) and recalled gamma interferon (IFN-), interleukin-2 (IL-2), IL-6, and IL-17 responses (P 0.05 or P 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log10 reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4 T cells producing protective cytokines, such as IFN- and IL-17, in lungs and spleens (P 0.01) and CD4 multifunctional T cells producing IFN-, tumor necrosis factor alpha (TNF-), and/or IL-17 (P 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN- production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses in vivo, may be informative for vaccine development, particularly in regions where the M. tuberculosis Beijing/K-strain is frequently isolated from TB patients.

Original languageEnglish
Article numbere00219-17
JournalClinical and Vaccine Immunology
Volume24
Issue number11
DOIs
Publication statusPublished - 2017 Nov 1

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Mycobacterium tuberculosis
Interleukin-17
Vaccines
Interferons
Immunization
T-Lymphocyte Epitopes
T-cells
Bacilli
Proteins
Lung
Bacillus
Spleen
Aerosols
Interferon-gamma
Interleukin-2
T-Lymphocytes
Interleukin-6
Republic of Korea
Bacterial Load
Tumor Necrosis Factor-alpha

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

Cite this

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title = "Protective vaccine efficacy of the complete form of PPE39 protein from mycobacterium tuberculosis Beijing/K strain in mice",
abstract = "The aim of this study was to evaluate the protective efficacy of MTBK_ 24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Gu{\'e}rin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (P 0.05) and recalled gamma interferon (IFN-), interleukin-2 (IL-2), IL-6, and IL-17 responses (P 0.05 or P 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log10 reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4 T cells producing protective cytokines, such as IFN- and IL-17, in lungs and spleens (P 0.01) and CD4 multifunctional T cells producing IFN-, tumor necrosis factor alpha (TNF-), and/or IL-17 (P 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN- production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses in vivo, may be informative for vaccine development, particularly in regions where the M. tuberculosis Beijing/K-strain is frequently isolated from TB patients.",
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Protective vaccine efficacy of the complete form of PPE39 protein from mycobacterium tuberculosis Beijing/K strain in mice. / Kim, Ahreum; Hur, Yun Gyoung; Gu, Sunwha; Cho, Sangnae.

In: Clinical and Vaccine Immunology, Vol. 24, No. 11, e00219-17, 01.11.2017.

Research output: Contribution to journalArticle

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