College of Veterinary Medicine, Henan Agricultural Universitygrid.108266.b, Zhengzhou, Henan, People's Republic of China.
International Joint Research Center of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural Universitygrid.108266.b, Zhengzhou, Henan, People's Republic of China.
Microbiol Spectr. 2022 Dec 21;10(6):e0287122. doi: 10.1128/spectrum.02871-22. Epub 2022 Nov 9.
Marek's disease virus (MDV) induces immunosuppression and neoplastic disease in chickens. The virus is controllable via an attenuated deletion mutant virus, which has the disadvantage of retaining the ability to induce lymphoid organ atrophy. To overcome this deficiency and produce more vaccine candidates, a recombinant MDV was generated from the highly virulent Md5BAC strain, in which both and a cytolytic replication-related gene, , were deleted. Replication of the double deletion virus, Md5BAC ΔΔ, was comparable with that of the parental virus . The double deletion virus was shown to be fully attenuated and to reduce lymphoid organ atrophy . Crucially, Md5BAC ΔΔ confers superior protection against highly virulent virus compared with a commercial vaccine strain, CVI988/Rispens. Transcriptomic profiling indicated that Md5BAC ΔΔ induced a different host immune response from CVI988/Rispens. In summary, a novel, effective, and safe vaccine candidate for prevention and control of MD caused by highly virulent MDV is reported. MDV is a highly contagious immunosuppressive and neoplastic pathogen. The virus can be controlled through vaccination via an attenuated deletion mutant virus that retains the ability to induce lymphoid organ atrophy. In this study, we overcame the deficiency by generating and double deletion mutant virus. Indeed, the successfully generated and double deletion mutant virus had significantly reduced replication capacity but not . It was fully attenuated and conferred superior protection efficacy against very virulent MDV challenge. In addition, the possible immunological protective mechanism of the double deletion mutant virus was shown to be different from that of the gold standard MDV vaccine, CVI988/Rispens. Overall, we successfully generated an attenuated deletion mutant virus and widened the range of potential vaccine candidates. Importantly, this study provides for the first time the theoretical basis of vaccination induced by fully attenuated gene-deletion mutant virus.
马立克氏病病毒（MDV）可引起鸡的免疫抑制和肿瘤疾病。该病毒可通过减毒缺失突变病毒进行控制，但这种病毒保留了诱导淋巴器官萎缩的能力。为了克服这一缺陷并生产更多的疫苗候选物，从高致病性 Md5BAC 株中生成了一种重组 MDV，其中 和一个细胞溶解复制相关基因 被删除。双缺失病毒 Md5BACΔΔ的复制与亲本病毒相当。结果表明，双缺失病毒完全减毒并减少了淋巴器官萎缩。至关重要的是，与商业疫苗株 CVI988/Rispens 相比，Md5BACΔΔ可提供针对高致病性病毒的卓越保护。转录组谱分析表明，Md5BACΔΔ诱导的宿主免疫反应与 CVI988/Rispens 不同。总之，报道了一种用于预防和控制由高致病性 MDV 引起的 MD 的新型、有效和安全的疫苗候选物。MDV 是一种高度传染性的免疫抑制和肿瘤病原体。该病毒可通过接种减毒 缺失突变病毒来控制，该病毒保留了诱导淋巴器官萎缩的能力。在这项研究中，我们通过生成 和 双缺失突变病毒克服了这一缺陷。实际上，成功生成的 和 双缺失突变病毒的复制能力显著降低，但 没有降低。它完全减毒并对非常高致病性 MDV 挑战提供了卓越的保护效果。此外，还表明双缺失突变病毒的可能免疫保护机制与金标准 MDV 疫苗 CVI988/Rispens 不同。总体而言，我们成功生成了一种减毒的 缺失突变病毒，并扩大了潜在疫苗候选物的范围。重要的是，这项研究首次为完全减毒基因缺失突变病毒接种提供了理论依据。
