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Vaccine. 2013 Oct 25;31(45):5202-9. doi: 10.1016/j.vaccine.2013.08.093. Epub 2013 Sep 20.

An adult zebrafish model for preclinical tuberculosis vaccine development.

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Institute of Biomedical Technology, BioMediTech, University of Tampere, FIN-33014 Tampere, Finland. Electronic address:


Tuberculosis remains a major global health challenge despite extensive vaccination schemes with the current live vaccine, Bacillus Calmette-Guérin. 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 low-dose (∼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.


CFU; Mycobacterium marinum; Tuberculosis; Vaccine; Zebrafish; colony forming unit; days post infection; dpi; weeks post infection; wpi

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