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表达水貂肠炎病毒样颗粒VP2蛋白的重组犬瘟热病毒可保护水貂免受这两种病毒的致死性攻击。

Recombinant canine distemper virus expressing virus-like particle VP2 protein of mink enteritis virus protects minks against lethal challenges of both viruses.

作者信息

Jiang Yuan, Sun Yiyang, Zhai Boyu, Chen Tianjie, Li Yang, Ren Lina, Ma Yuchen, Han Kun, Wang Jianke, Bi Zhenwei, Hu Bo, Zhao Jianjun

机构信息

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.

College of Veterinary Medicine, Hebei Agricultural University, Baoding, China.

出版信息

Vet Microbiol. 2025 Aug;307:110625. doi: 10.1016/j.vetmic.2025.110625. Epub 2025 Jun 26.

Abstract

Canine distemper virus (CDV) and mink enteritis virus (MEV) are among the most devastating viruses in minks (Mustela vison). They often cause two fatal diseases-canine distemper (CD) and mink viral enteritis (MVE)-resulting in severe respiratory symptoms and acute enteritis in breeding minks, respectively. Here, using the attenuated CDV vaccine strain CDV3-CL (currently employed in breeding mink in China) as a backbone, we constructed a recombinant strain, rCDV3-mVP2, expressing the wild-type MEV capsid protein VP2. Notably, the VP2 protein expressed by this recombinant virus assembles into virus-like particles (VLPs) in Vero cells and exhibits hemagglutination activity. rCDV3-mVP2 exhibits genetic stability through at least 30 serial passages and replicates to titers comparable to the parental CDV3-CL strain in Vero cells. To evaluate its protective efficacy as a bivalent vaccine candidate, twenty weaned minks were immunized with rCDV3-mVP2 (10 TCID) and challenged with a highly virulent CDV strain (SD (14)7; n = 5 minks) or lethal MEV wild-type strain (LN-10; n = 5 minks) 3 weeks post-immunization. A single vaccination with rCDV3-mVP2 induced neutralizing antibodies (mean value = 43) against CDV and hemagglutination-inhibiting antibodies (mean value = 128) against MEV, conferring 100 % protection against lethal challenges of both viruses. Moreover, vaccination effectively alleviated lymphopenia, reduced virus shedding, and minimized tissue viral loads and pathological changes. These results suggest that rCDV-mVP2 is a suitable bivalent live vaccine against CDV and MEV for minks. IMPORTANCE: Canine distemper (CD) and mink viral enteritis (MVE), caused by canine distemper virus (CDV) and mink enteritis virus (MEV), respectively, are fatal diseases in minks, with significant impacts on the mink product industry. In this study, we employed reverse genetics to construct a recombinant CDV vaccine strain, rCDV3-mVP2, that expresses stably the MEV VP2 protein. Vaccination of weaned minks with rCDV3-mVP2 safely induced neutralizing antibody responses to both viruses, protecting minks from challenges with lethal CDV and MEV. This is the first study to demonstrate that recombinant CDV can be serve as a bivalent live vaccine for MVE and CD in animals.

摘要

犬瘟热病毒(CDV)和水貂肠炎病毒(MEV)是水貂(Mustela vison)中最具毁灭性的病毒。它们常引发两种致命疾病——犬瘟热(CD)和水貂病毒性肠炎(MVE),分别导致种用水貂出现严重呼吸道症状和急性肠炎。在此,我们以减毒的CDV疫苗株CDV3-CL(目前在中国种用水貂中使用)为基础,构建了一种表达野生型MEV衣壳蛋白VP2的重组毒株rCDV3-mVP2。值得注意的是,这种重组病毒表达的VP2蛋白在Vero细胞中组装成病毒样颗粒(VLP)并表现出血凝活性。rCDV3-mVP2在至少30次连续传代后表现出遗传稳定性,并且在Vero细胞中的复制滴度与亲本CDV3-CL毒株相当。为了评估其作为二价疫苗候选物的保护效力,20只断奶水貂用rCDV3-mVP2(10 TCID)免疫,并在免疫后3周用高毒力CDV毒株(SD(14)7;n = 5只水貂)或致死性MEV野生型毒株(LN-10;n = 5只水貂)进行攻毒。单次接种rCDV3-mVP2诱导产生了针对CDV的中和抗体(平均值 = 43)和针对MEV的血凝抑制抗体(平均值 = 128),对两种病毒的致死性攻毒均提供了100%的保护。此外,接种疫苗有效缓解了淋巴细胞减少,减少了病毒排出,并使组织病毒载量和病理变化最小化。这些结果表明,rCDV-mVP2是一种适用于水貂的抗CDV和MEV的二价活疫苗。重要性:分别由犬瘟热病毒(CDV)和水貂肠炎病毒(MEV)引起的犬瘟热(CD)和水貂病毒性肠炎(MVE)是水貂的致命疾病,对水貂产品行业有重大影响。在本研究中,我们利用反向遗传学构建了一种重组CDV疫苗株rCDV3-mVP2,其稳定表达MEV VP2蛋白。用rCDV3-mVP2对断奶水貂进行接种可安全诱导对两种病毒的中和抗体反应,保护水貂免受致死性CDV和MEV的攻毒。这是首次证明重组CDV可作为动物MVE和CD的二价活疫苗的研究。

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