title: Pulmonary immunity and durable protection induced by the ID93/GLA-SE vaccine candidate against the hyper-virulent Korean Beijing Mycobacterium tuberculosis strain K.
abstract: 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.
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Seung Bin
authors.initials: SB
authors.lastname: Cha
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Kee Woong
authors.initials: KW
authors.lastname: Kwon
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Seung Jung
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: raycho@yuhs.ac.
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102, USA.
authors.forename: Rhea N
authors.initials: RN
authors.lastname: Coler
authors.affiliation: Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: sjshin@yuhs.ac.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D000818:Animals; D058491:Bacterial Load; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000145:classification; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D007376:Interleukin-2; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Beijing family; GLA-SE; ID93; K strain; Tuberculosis