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Pulmonary immunity and durable protection induced by the ID93/GLA-SE vaccine candidate against the hyper-virulent Korean Beijing Mycobacterium tuberculosis strain K

 Seung Bin Cha  ;  Woo Sik Kim  ;  Jong-Seok Kim  ;  Hongmin Kim  ;  Kee Woong Kwon  ;  Seung Jung Han  ;  Sang-Nae Cho  ;  Rhea N. Coler  ;  Steven G. Reed  ;  Sung Jae Shin 
 VACCINE, Vol.34(19) : 2179-2187, 2016 
Journal Title
Issue Date
Animals ; Bacterial Load ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Female ; Immunologic Memory ; Interferon-gamma/immunology ; Interleukin-2/immunology ; Lung/immunology* ; Lung/microbiology ; Lung/pathology ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/classification ; Spleen/immunology ; Spleen/microbiology ; Tuberculosis/immunology ; Tuberculosis/prevention & control* ; Tuberculosis Vaccines/immunology* ; Tumor Necrosis Factor-alpha/immunology
Beijing family ; GLA-SE ; ID93 ; K strain ; Tuberculosis
The majority of tuberculosis (TB) vaccine candidates advanced to clinical trials have been evaluated preclinically using laboratory-adapted strains. However, it has been proposed that challenge with clinical isolates in preclinical vaccine testing could provide further and more practical validation. Here, we tested the ID93/GLA-SE TB vaccine candidate against the clinical Mycobacterium tuberculosis (Mtb) strain K (Mtb K) belonging to the Beijing family, the most prevalent Mtb strain in South Korea. Mice immunized with ID93/GLA-SE exhibited a significant reduction in bacteria and reduced lung inflammation against Mtb K when compared to non-immunized controls. In addition, we analyzed the immune responses in the lungs of ID93/GLA-SE-immunized mice, and showed that ID93/GLA-SE was able to elicit sustained Th1-biased immune responses including antigen-specific multifunctional CD4(+) T cell co-producing IFN-γ, TNF-α, and IL-2 as well as a high magnitude of IFN-γ response for up to 10 weeks post-challenge. Notably, further investigation of T cell subsets in the lung following challenge showed remarkable generation of CD8(+) central memory T cells by ID93/GLA-SE-immunization. Our findings showed that ID93/GLA-SE vaccine confers a high level of robust protection against the hypervirulent Mtb Beijing infection which was characterized by pulmonary Th1-polarized T-cell immune responses. These findings may also provide relevant information for potential utility of this vaccine candidate in East-Asian countries where the Beijing genotype is highly prevalent.
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5. Research Institutes (연구소) > Institute for Immunology and Immunological Disease (면역질환연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Seok(김종석)
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Cho, Sang Nae(조상래)
Cha, Seung Bin(차승빈)
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