Song Cuiping, Yang Yang, Hu Jing, Yu Shengqing, Sun Yingjie, Qiu Xvsheng, Tan Lei, Meng Chunchun, Liao Ying, Liu Weiwei, Ding Chan
Shanghai Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Ziyue Road 518, Shanghai 200241, China.
Vaccines (Basel). 2020 Jul 20;8(3):399. doi: 10.3390/vaccines8030399.
Recently, chickens vaccinated with the CVI988/Rispens vaccine showed increased tumor incidence. Moreover, many strains of Marek's disease virus (MDV) that were naturally integrated with the long terminal repeat (LTR) of the avian reticuloendotheliosis virus (REV) have been isolated, which means it is necessary to develop a new vaccine. In this study, two LTR sequences were inserted into Rispens to construct a recombinant MDV (rMDV). Then, the safety and efficacy of rMDV were evaluated separately in chickens. The growth rate curves showed that the insertion of REV-LTR into MDV enabled a faster replication in vitro than Rispens. Chickens immunized with high or repeated dose rMDV had no MD clinical signs. Further, no tumor, tissue lesions, or evident pathological changes were observed in the chicken organs. Polymerase chain reaction (PCR) and virus isolation revealed that rMDV had the ability to spread horizontally to non-immunized chickens and had no impact on the environment. After five passages in chickens, there were no obvious lesions, and the LTR insertion was stable. There were also no deletions or mutations, which indicates that rMDV is safe in chickens. In addition, rMDV has an advantage over Rispens against vvMDV Md5 at low doses. All results demonstrate that the transgenic strain of rMDV with REV-LTR can be used as a live attenuated vaccine candidate.
最近，接种CVI988/Rispens疫苗的鸡群肿瘤发病率有所上升。此外，已经分离出许多与禽网状内皮组织增生症病毒（REV）的长末端重复序列（LTR）自然整合的马立克氏病病毒（MDV）毒株，这意味着有必要研发一种新疫苗。在本研究中，将两个LTR序列插入Rispens中以构建重组MDV（rMDV）。然后，分别在鸡群中评估rMDV的安全性和有效性。生长速率曲线表明，将REV-LTR插入MDV后，其在体外的复制速度比Rispens更快。用高剂量或重复剂量rMDV免疫的鸡没有MD临床症状。此外，在鸡的器官中未观察到肿瘤、组织病变或明显的病理变化。聚合酶链反应（PCR）和病毒分离显示，rMDV有水平传播至未免疫鸡的能力，且对环境没有影响。在鸡体内传代五次后，没有明显病变，LTR插入稳定。也没有缺失或突变，这表明rMDV在鸡体内是安全的。此外，在低剂量下，rMDV相对于Rispens对vvMDV Md5具有优势。所有结果表明，带有REV-LTR的rMDV转基因株可作为一种活疫苗候选株。
