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B cell-based vaccine transduced with esat6-expressing vaccinia virus and presenting α-galactosylceramide is a novel vaccine candidate against esat6-expressing mycobacterial diseasesoa mark
  • Kwon, Bo Eun ;
  • Ahn, Jae Hee ;
  • Park, Eun Kyoung ;
  • Jeong, Hyunjin ;
  • Lee, Hyo Ji ;
  • Jung, Yu Jin ;
  • Shin, Sung Jae ;
  • Jeong, Hye Sook ;
  • Yoo, Jung Sik ;
  • Shin, Eunkyoung ;
  • Yeo, Sang Gu ;
  • Chang, Sun Young ;
  • Ko, Hyun Jeong
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Publication Year
2019-01-01
Journal
Frontiers in Immunology
Publisher
Frontiers Media S.A.
Citation
Frontiers in Immunology, Vol.10 No.OCT
Keyword
ESAT6Mycobacterium kansasiiMycobacterium tuberculosisNon-tuberculous mycobacteriaVaccineα-galactosylceramide
Mesh Keyword
AnimalsAntibodies, BacterialAntigen PresentationAntigens, BacterialB-LymphocytesBacterial ProteinsCytokinesDisease Models, AnimalGalactosylceramidesGene ExpressionImmunizationMiceT-Lymphocyte SubsetsTuberculosisTuberculosis VaccinesVaccinia virus
All Science Classification Codes (ASJC)
Immunology and AllergyImmunology
Abstract
Early secretory antigenic target-6 (ESAT6) is a potent immunogenic antigen expressed in Mycobacterium tuberculosis as well as in some non-tuberculous mycobacteria (NTM), such as M. kansasii. M. kansasii is one of the most clinically relevant species of NTM that causes mycobacterial lung disease, which is clinically indistinguishable from tuberculosis. In the current study, we designed a novel cell-based vaccine using B cells that were transduced with vaccinia virus expressing ESAT6 (vacESAT6), and presenting α-galactosylceramide (αGC), a ligand of invariant NKT cells. We found that B cells loaded with αGC had increased levels of CD80 and CD86 after in vitro stimulation with NKT cells. Immunization of mice with B/αGC/vacESAT6 induced CD4+ T cells producing TNF-α and IFN-γ in response to heat-killed M. tuberculosis. Immunization of mice with B/αGC/vacESAT6 ameliorated severe lung inflammation caused by M. kansasii infection. We also confirmed that immunization with B/αGC/vacESAT6 reduced M. kansasii bacterial burden in the lungs. In addition, therapeutic administration of B/αGC/vacESAT6 increased IFN-γ+ CD4+ T cells and inhibited the progression of lung pathology caused by M. kansasii infection. Thus, B/αGC/vacESAT6 could be a potent vaccine candidate for the prevention and treatment of ESAT6-expressing mycobacterial infection caused by M. kansasii.
ISSN
1664-3224
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/30995
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074561901&origin=inward
DOI
https://doi.org/2-s2.0-85074561901
Journal URL
https://www.frontiersin.org/journals/immunology#
Type
Article
Funding
This research was supported by a grant from the Korean Health Technology R&D Projects, Ministry of Health & Welfare, Republic of Korea (HI15C0450) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2017R1A2B2001963, NRF-2017M3A9C8060390).This research was supported by a grant from the Korean Health Technology R&D Projects, Ministry of Health & Welfare, Republic of Korea (HI15C0450) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2017R1A2B2001963, NRF-2017M3A9C8060390). We thank Byung-Il Yoon, College of Veterinary Medicine and Institute of Veterinary Science at Kangwon National University for providing technical assistance for histopathological examinations.
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