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.
Bibliographical noteFunding Information:
This work was supported by Basic Science Research Program and the International Research & Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning ( NRF-2013R1A2A1A01009932 and NRF-2014K1A3A7A03075054 ) and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea ( HR14C0006 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was also supported by National Institutes of Health grants AI-078054 .
© 2016 Elsevier Ltd.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Immunology and Microbiology(all)
- Public Health, Environmental and Occupational Health
- Infectious Diseases