Dai Zhenkai, Huang Jianfei, Lei Xiaoya, Yan Yiming, Lu Piaopiao, Zhang Huanmin, Lin Wencheng, Chen Weiguo, Ma Jingyun, Xie Qingmei
College of Animal Science, South China Agricultural University & Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding & Key Laboratory of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture, Guangzhou 510642, PR China; Key Laboratory of Animal Health Aquaculture and Environmental Control, Guangzhou, Guangdong 510642, PR China.
USDA, Agriculture Research Service, Avian Disease and Oncology Laboratory, East Lansing, MI 48823, USA.
Vaccine. 2017 Feb 1;35(5):808-813. doi: 10.1016/j.vaccine.2016.12.034. Epub 2016 Dec 31.
Infection with the avian leukosis virus subgroup J (ALV-J) can lead to neoplastic disease in chickens, inflicting significant economic losses to the poultry industry. Recent reports have identified inhibitory effects of ALV-J on autophagy, a process involving in innate and adaptive immunity. Inspired by this connection between autophagy and immunity, we developed a novel DNA vaccine against ALV-J which includes co-administration of rapamycin to stimulate autophagy. To measure the efficacy of the developed prototype vaccine, five experimental groups of seven-day-old chickens was immunized three times at three-week intervals respectively with vector, pVAX1-gp85, pVAX1-gp85-LC3, pVAX1-gp85+rapamycin and pVAX1-gp85-LC3+rapamycin through electroporation. We then tested their antibody titers, cytokine levels and cellular immune responses. The immunoprotective efficacy of the prototype vaccines against the challenge of the ALV-J GD1109 strain was also examined. The results showed that the combination of pVAX1-gp85-LC3 and rapamycin was able to induce the highest antibody titers, and enhance interleukin(IL)-2, IL-10 and interferon (IFN)-γ expression, and the chickens immunized with the combination of pVAX1-gp85-LC3 and rapamycin showed the highest percentage of CD3+CD8+T lymphocytes. Based on our results, we suggest that stimulating autophagy can improve the efficacy of DNA vaccines and that our DNA vaccine shows the potential of being a candidate vaccine against ALV-J. This study provides a novel strategy for developing vaccines against ALV-J.
感染禽白血病病毒J亚群（ALV-J）可导致鸡发生肿瘤性疾病，给家禽业造成重大经济损失。最近的报告发现ALV-J对自噬有抑制作用，自噬是一个涉及固有免疫和适应性免疫的过程。受自噬与免疫之间这种联系的启发，我们开发了一种新型抗ALV-J DNA疫苗，其中包括联合使用雷帕霉素来刺激自噬。为了测量所开发的原型疫苗的效力，将五组七日龄鸡分别以三周的间隔通过电穿孔用载体、pVAX1-gp85、pVAX1-gp85-LC3、pVAX1-gp85+雷帕霉素和pVAX1-gp85-LC3+雷帕霉素免疫三次。然后我们检测了它们的抗体滴度、细胞因子水平和细胞免疫反应。还检查了原型疫苗对ALV-J GD1109株攻击的免疫保护效力。结果表明，pVAX1-gp85-LC3和雷帕霉素的组合能够诱导最高的抗体滴度，增强白细胞介素（IL）-2、IL-10和干扰素（IFN）-γ的表达，并且用pVAX1-gp85-LC3和雷帕霉素组合免疫的鸡显示出最高百分比的CD3+CD8+T淋巴细胞。基于我们的结果，我们建议刺激自噬可以提高DNA疫苗的效力，并且我们的DNA疫苗显示出成为抗ALV-J候选疫苗的潜力。本研究为开发抗ALV-J疫苗提供了一种新策略。
