B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases
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, whi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02542/full |
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| author | Bo-Eun Kwon Jae-Hee Ahn Eun-Kyoung Park Hyunjin Jeong Hyo-Ji Lee Yu-Jin Jung Sung Jae Shin Hye-Sook Jeong Jung Sik Yoo EunKyoung Shin Sang-Gu Yeo Sun-Young Chang Hyun-Jeong Ko |
| author_facet | Bo-Eun Kwon Jae-Hee Ahn Eun-Kyoung Park Hyunjin Jeong Hyo-Ji Lee Yu-Jin Jung Sung Jae Shin Hye-Sook Jeong Jung Sik Yoo EunKyoung Shin Sang-Gu Yeo Sun-Young Chang Hyun-Jeong Ko |
| author_sort | Bo-Eun Kwon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T07:03:06Z |
| format | Article |
| id | doaj.art-882b3c8d0ddf46ba8c2d9dbe2495e746 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T07:03:06Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-882b3c8d0ddf46ba8c2d9dbe2495e7462022-12-21T23:55:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02542482699B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial DiseasesBo-Eun Kwon0Jae-Hee Ahn1Eun-Kyoung Park2Hyunjin Jeong3Hyo-Ji Lee4Yu-Jin Jung5Sung Jae Shin6Hye-Sook Jeong7Jung Sik Yoo8EunKyoung Shin9Sang-Gu Yeo10Sun-Young Chang11Hyun-Jeong Ko12Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South KoreaLaboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South KoreaLaboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South KoreaLaboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South KoreaDepartment of Biological Sciences, Kangwon National University, Chuncheon, South KoreaDepartment of Biological Sciences, Kangwon National University, Chuncheon, South KoreaDepartment of Microbiology, Institute for Immunology and Immunological Disease, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South KoreaDivision of Vaccine Research, Center for Infectious Disease Research, Korea National Institute of Health (KNIH), Korea Centers for Disease Control and Prevention (KCDC), Cheongju, South KoreaDivision of Vaccine Research, Center for Infectious Disease Research, Korea National Institute of Health (KNIH), Korea Centers for Disease Control and Prevention (KCDC), Cheongju, South KoreaDivision of Vaccine Research, Center for Infectious Disease Research, Korea National Institute of Health (KNIH), Korea Centers for Disease Control and Prevention (KCDC), Cheongju, South KoreaSejong Institute of Health and Environment, Sejong, South KoreaLaboratory of Microbiology, College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, South KoreaLaboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, South KoreaEarly 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.02542/fullMycobacterium kansasiiMycobacterium tuberculosisnon-tuberculous mycobacteriaESAT6vaccineα-galactosylceramide |
| spellingShingle | Bo-Eun Kwon Jae-Hee Ahn Eun-Kyoung Park Hyunjin Jeong Hyo-Ji Lee Yu-Jin Jung Sung Jae Shin Hye-Sook Jeong Jung Sik Yoo EunKyoung Shin Sang-Gu Yeo Sun-Young Chang Hyun-Jeong Ko B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases Frontiers in Immunology Mycobacterium kansasii Mycobacterium tuberculosis non-tuberculous mycobacteria ESAT6 vaccine α-galactosylceramide |
| title | B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases |
| title_full | B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases |
| title_fullStr | B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases |
| title_full_unstemmed | B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases |
| title_short | B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases |
| title_sort | b cell based vaccine transduced with esat6 expressing vaccinia virus and presenting α galactosylceramide is a novel vaccine candidate against esat6 expressing mycobacterial diseases |
| topic | Mycobacterium kansasii Mycobacterium tuberculosis non-tuberculous mycobacteria ESAT6 vaccine α-galactosylceramide |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02542/full |
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