Vaccine efficacy of a Mycobacterium tuberculosis Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates

Kee Woong Kwon, Hong Hee Choi, Seung Jung Han, Jong Seok Kim, Woo Sik Kim, Hongmin Kim, Lee Han Kim, Soon Myung Kang, Jaehun Park, SungJae Shin

Research output: Contribution to journalArticle

Abstract

Bacillus Calmette-Guerin vaccine confers insufficient pulmonary protection against tuberculosis (TB), particularly the Mycobacterium tuberculosis (Mtb) Beijing strain infection. Identification of vaccine antigens (Ags) by considering Mtb genetic diversity is crucial for the development of improved TB vaccine. MTBK_20640, a new Beijing genotype-specific proline-glutamic acid-family Ag, was identified by comparative genomic analysis. Its immunologic features were characterized by evaluating interactions with dendritic cells (DCs), and immunogenicity and vaccine efficacy were determined against highly virulent Mtb Beijing outbreak Korean Beijing (K) strain and HN878 strain in murine infection model. MTBK_20640 induced DCs via TLR2 and downstream MAPK and NF-κB signaling pathways, effectively promoting naive CD4-positive (CD4+) T-cell proliferation and IFN-γ production. Different IFN-γ response was observed in mice infected with Mtb K or reference H37Rv strain. Significant induction of T helper type 1 cell-polarized Ag-specific multifunctional CD4+ T cells and a marked Ag-specific IgG2c response were observed in mice immunized with MTBK_20640/glucopyranosyl lipid adjuvant-stable emulsion. The immunization conferred long-term protection against 2 Mtb Beijing outbreak strains, as evidenced by a significant reduction in colony-forming units in the lung and spleen and reduced lung inflammation. MTBK_20640 vaccination conferred long-term protection against highly virulent Mtb Beijing strains. MTBK_20640 may be developed into a novel Ag component in multisubunit TB vaccines in the future.-Kwon, K. W., Choi, H.-H., Han, S. J., Kim, J.-S., Kim, W. S., Kim, H., Kim, L.-H., Kang, S. M., Park, J., Shin, S. J. Vaccine efficacy of a Mycobacterium tuberculosis Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates.

Original languageEnglish
Pages (from-to)6483-6496
Number of pages14
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number5
DOIs
Publication statusPublished - 2019 May 1

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Mycobacterium tuberculosis
Proline
Disease Outbreaks
Glutamic Acid
Vaccines
Antigens
Tuberculosis Vaccines
T-cells
Dendritic Cells
Immunization
BCG Vaccine
T-Lymphocytes
Cell proliferation
Lung
Th1 Cells
Emulsions
Infection
Beijing
Pneumonia
Vaccination

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Kwon, Kee Woong ; Choi, Hong Hee ; Han, Seung Jung ; Kim, Jong Seok ; Kim, Woo Sik ; Kim, Hongmin ; Kim, Lee Han ; Kang, Soon Myung ; Park, Jaehun ; Shin, SungJae. / Vaccine efficacy of a Mycobacterium tuberculosis Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 5. pp. 6483-6496.
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Vaccine efficacy of a Mycobacterium tuberculosis Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates. / Kwon, Kee Woong; Choi, Hong Hee; Han, Seung Jung; Kim, Jong Seok; Kim, Woo Sik; Kim, Hongmin; Kim, Lee Han; Kang, Soon Myung; Park, Jaehun; Shin, SungJae.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 5, 01.05.2019, p. 6483-6496.

Research output: Contribution to journalArticle

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AU - Kwon, Kee Woong

AU - Choi, Hong Hee

AU - Han, Seung Jung

AU - Kim, Jong Seok

AU - Kim, Woo Sik

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