Journal
VACCINE
Volume 31, Issue 45, Pages 5202-5209Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2013.08.093
Keywords
Zebrafish; Tuberculosis; Vaccine; Mycobacterium marinum
Categories
Funding
- Academy of Finland [121003, 139225]
- Jane and Aatos Erkko Foundation
- Sigrid Juselius Foundation
- Competitive Research Funding of the Tampere University Hospital
- Tampere Tuberculosis Foundation
- Foundation of the Finnish Anti-Tuberculosis Association
- Finnish Cultural Foundation
- Pirkanmaa Regional Fund
- Jalmari and Rauha Ahokas Foundation
- Wino and Laina Kivi Foundation
- Academy of Finland (AKA) [121003, 139225, 139225, 121003] Funding Source: Academy of Finland (AKA)
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Tuberculosis remains a major global health challenge despite extensive vaccination schemes with the current live vaccine, Bacillus Calmette-Guerin. Tuberculosis vaccine research has been hampered by a scarcity of animal models which replicate human disease and are suitable for large-scale studies. We have shown recently that Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, causes an infection resembling human tuberculosis in adult zebrafish (Danio rerio). In the present study we use this model to show that BCG vaccination as well as DNA vaccination with selected mycobacterial antigens (Ag85B, CFP-10 and ESAT-6) protects adult zebrafish from mycobacterial infection. Using a lowdose (similar to 20-30 bacteria) intraperitoneal M. marinum infection, both the number of granulomas and the amount of infected organs were reduced in the DNA vaccinated fish. Likewise, when infecting with a lethal infection dose (-20,000-27,000 bacteria), vaccination significantly reduced both mortality and bacterial counts in a manner dependent on the adaptive immune response. Protective effects of vaccination were associated with enhanced expression of interferon gamma. Our results indicate that the zebrafish is a promising new model for preclinical tuberculosis vaccine research. (C) 2013 Elsevier Ltd. All rights reserved.
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