Oksanen Kaisa E, Myllymäki Henna, Ahava Maarit J, Mäkinen Leena, Parikka Mataleena, Rämet Mika
BioMediTech, University of Tampere, FIN 33014, Tampere, Finland.
BioMediTech, University of Tampere, FIN 33014, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, FIN 33521, Tampere, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland; PEDEGO Research Unit, and Medical Research Center Oulu, University of Oulu, Oulu, Finland.
Dev Comp Immunol. 2016 Jan;54(1):89-96. doi: 10.1016/j.dci.2015.09.001. Epub 2015 Sep 9.
Despite the widespread use of the current Bacillus Calmette-Guérin (BCG) vaccine, tuberculosis is still a major cause of morbidity and mortality worldwide. Vaccination with BCG does not prevent a Mycobacterium tuberculosis infection, nor does it inhibit the reactivation of latent tuberculosis. Here, we show that adult zebrafish are modestly and variably protected from a mycobacterial infection by BCG vaccination. An intraperitoneal (i.p.) BCG vaccination was associated with enhanced survival upon a high-dose (20,000 bacteria) Mycobacterium marinum infection. In addition, BCG-vaccinated fish were more able to restrict a low-dose (30 bacteria) intraperitoneal infection with M. marinum, as indicated by lower bacterial loads at six weeks post infection (wpi). However, the vaccination could not completely prevent an infection. A qRT-PCR analysis comparing BCG-vaccinated and unvaccinated fish upon a mycobacterial infection indicated that the induction of Tumor necrosis factor (TNF) was more modest in vaccinated fish. The partial protection gained by BCG could be boosted by a DNA vaccine combining Ag85B, ESAT6 and a resuscitation-related gene RpfE, suggesting that this combination of antigens could be useful for a future BCG booster vaccine. We conclude that zebrafish is a useful early-phase preclinical model for studying subunit vaccines designed for boosting the effects of BCG.
尽管目前广泛使用卡介苗（BCG），但结核病仍是全球发病和死亡的主要原因。接种卡介苗并不能预防结核分枝杆菌感染，也不能抑制潜伏性结核病的复发。在此，我们表明成年斑马鱼通过卡介苗接种可获得适度且可变的抗分枝杆菌感染保护。腹腔内（i.p.）接种卡介苗与在高剂量（20,000个细菌）海分枝杆菌感染后存活率提高有关。此外，接种卡介苗的鱼更能限制低剂量（30个细菌）腹腔内海分枝杆菌感染，感染后六周（wpi）时细菌载量较低表明了这一点。然而，接种疫苗并不能完全预防感染。一项比较接种和未接种卡介苗的鱼在分枝杆菌感染后的qRT-PCR分析表明，接种疫苗的鱼中肿瘤坏死因子（TNF）的诱导作用较弱。结合Ag85B、ESAT6和复苏相关基因RpfE的DNA疫苗可增强卡介苗获得的部分保护作用，这表明这种抗原组合可能对未来的卡介苗加强疫苗有用。我们得出结论，斑马鱼是研究旨在增强卡介苗效果的亚单位疫苗的有用早期临床前模型。
