A highly efficient recombinant canarypox virus-based vaccine against canine distemper virus constructed using the CRISPR/Cas9 gene editing method
A highly efficient recombinant canarypox virus-based vaccine against canine distemper virus constructed using the CRISPR/Cas9 gene editing method
复制标题
利用CRISPR/Cas9基因编辑方法构建的高效重组金丝雀痘病毒疫苗，对抗犬瘟热病毒
DOI：
10.1016/j.vetmic.2020.108920
复制
发表时间：
2020-12-01
影响因子：
3.3
通讯作者：
Xia, Xianzhu
中科院分区：
文献类型：
--
作者：
Gong, Yuchen;Chen, Tingwei;Xia, Xianzhu
犬瘟热病毒（CDV）是犬瘟热（CD）的病原，是影响野生和家养食肉动物的重要传染病之一。疫苗接种是预防犬瘟热在家养食肉动物中感染的有效方法。含有CDV血凝素（H）和融合（F）基因的Canarypox载体重组CD疫苗（如Recombitek CDV、PureVax Ferret Distemper和Merial）可在犬和雪貂中诱导有效的免疫应答。然而，疫苗的有效性因物种而异。在当前的研究中，我们开发了一种高效的重组金丝雀痘病毒，称为“ALVAC-CDV-M-F-H/C5-”，其通过使用CRISPR/Cas9基因编辑方法包含CDV病毒样颗粒（VLP），这使得基质（M），H和F基因能够同时表达。重组菌株提供了更快的血清转化比亲本菌株之间的水貂，以及提供了更高的抗体阳性率比亲本菌株之间的狐狸和水貂，甚至在管理的第二次加强疫苗接种。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，并且产生CDV VLP的高剂量新重组菌株可能会带来良好的结果在预防狐狸和水貂CD方面。
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.