期刊
TUBERCULOSIS
卷 113, 期 -, 页码 65-75出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.tube.2018.07.003
关键词
Tuberculosis; DNA vaccine; BERopt; BCG; Mycobacterium tuberculosis
资金
- University Development Fund of the University of Hong Kong
- Li Ka Shing Faculty of Medicine Matching Fund
- San-Ming Project of Medicine in Shenzhen
- China's NSFC [81172886]
- Hong Kong Health and Medical Research Fund [HMRF11101022]
DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BERopt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BERopt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer(+) CD8(+) T cells in peripheral blood and IFN-gamma-secreting CD8(+) T cells in splenocytes. Meanwhile, the BERopt vaccine-induced long-lasting T cell immunity protected BALB/c mice from high dose viral challenge using a modified vaccinia virus Tiantan strain expressing mature Ag85B protein (MVTT-m85B) and the virulent M. tb H37Rv aerosol challenge. Since the BERopt DNA vaccine does not induce anti-vector immunity, the strong immunogenicity and protective efficacy of this novel DNA vaccine warrant its future development for M. tb prevention and immunotherapy to alleviate the global TB burden.
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