An adult zebrafish model for preclinical tuberculosis vaccine development.
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.
Institute of Biomedical Technology, BioMediTech, University of Tampere, FIN-33014 Tampere, Finland. Electronic address: kaisa.oksanen@uta.fi.
Kaisa E
KE
Oksanen
Nicholas J A
NJ
Halfpenny
Eleanor
E
Sherwood
Sanna-Kaisa E
SK
Harjula
Milka M
MM
Hammarén
Maarit J
MJ
Ahava
Elina T
ET
Pajula
Marika J
MJ
Lahtinen
Mataleena
M
Parikka
Mika
M
Rämet
D000818:Animals; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019910:Mycobacterium marinum / Q000276:immunology* / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016019:Survival Analysis; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D015027:Zebrafish
D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma
CFU; Mycobacterium marinum; Tuberculosis; Vaccine; Zebrafish; colony forming unit; days post infection; dpi; weeks post infection; wpi