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, Sung Jae Shin

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3 Citations (Scopus)

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. FASEB J. 33, 6483–6496 (2019). www.fasebj.org.

Original languageEnglish
Pages (from-to)6483-6496
Number of pages14
JournalFASEB Journal
Volume33
Issue number5
DOIs
Publication statusPublished - 2019 May 1

Bibliographical note

Funding Information:
The authors thank Professor Sang-Jun Ha from the College of Life Science and Biotechnology, Department of Biochemistry, Yonsei University, for his helpful advice on the experimental design and technical support. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of science, ICT & Future Planning (NRF-2016R1A2A1A05005263) and by a grant from the Korean Health Technology R&D Project of the Ministry of Health & Welfare (HI17C0175), Republic of Korea. The authors declare no conflicts of interest.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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