College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China.
College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, 130122, China.
Vet Microbiol. 2020 Dec;251:108920. doi: 10.1016/j.vetmic.2020.108920. Epub 2020 Nov 5.
Canine distemper virus (CDV) is the causative agent of canine distemper (CD), which is one of the most important infectious diseases affecting wild and domestic carnivores. Vaccination represents an effective approach to prevent CDV infection among domestic carnivores. Canarypox-vectored recombinant CD vaccines (such as Recombitek CDV, PureVax Ferret Distemper, and Merial) with the CDV hemagglutinin (H) and fusion (F) genes can induce a potent immune response in dogs and ferrets. However, the vaccine's effectiveness varies with the species. In the current study, we developed a highly efficient recombinant canarypox virus termed as "ALVAC-CDV-M-F-H/C5" that contained CDV virus-like particles (VLPs) by using the CRISPR/Cas9 gene editing method, which enabled concurrent expression of the matrix (M), H, and F genes. The recombinant strain provided faster seroconversion than the parent strain among minks as well as provided higher rates of antibody positivity than the parent strain among foxes and minks even before the administration of a second booster vaccination. We demonstrated, for the first time, that the CRISPR/Cas9 system can be applied for the rapid and efficient modification of the ALVAC-CDV-F-H genome and also that a high-dose new recombinant strain that produces CDV VLPs may present good outcomes in the prevention of CD among foxes and minks.
犬瘟热病毒（CDV）是犬瘟热（CD）的病原体，是影响野生和家养食肉动物的最重要传染病之一。疫苗接种是预防家养食肉动物 CDV 感染的有效方法。含有 CDV 血凝素（H）和融合（F）基因的金丝雀痘载体重组 CD 疫苗（如 Recombitek CDV、PureVax 雪貂犬瘟热疫苗和梅里亚）可在犬和雪貂中诱导强烈的免疫反应。然而，疫苗的有效性因物种而异。在本研究中，我们使用 CRISPR/Cas9 基因编辑方法开发了一种高效的重组金丝雀痘病毒，称为“ALVAC-CDV-M-F-H/C5”，它包含 CDV 病毒样颗粒（VLPs），能够同时表达基质（M）、H 和 F 基因。与亲本株相比，重组株在水貂中更快地产生血清转化，在狐狸和水貂中更早地产生抗体阳性率，甚至在第二次加强免疫接种之前也是如此。我们首次证明，CRISPR/Cas9 系统可用于快速有效地修饰 ALVAC-CDV-F-H 基因组，并且高剂量的新重组株产生 CDV VLPs 可能在预防狐狸和水貂的 CD 方面具有良好的效果。
