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从大肠杆菌表达的犬细小病毒衣壳蛋白的病毒样颗粒的自组装及其作为病毒样颗粒疫苗的应用。

Self-assembly of virus-like particles of canine parvovirus capsid protein expressed from Escherichia coli and application as virus-like particle vaccine.

作者信息

Xu Jin, Guo Hui-Chen, Wei Yan-Quan, Dong Hu, Han Shi-Chong, Ao Da, Sun De-Hui, Wang Hai-Ming, Cao Sui-Zhong, Sun Shi-Qi

机构信息

State Key Laboratory of Veterinary Etiological Biology and National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu, 730046, China.

出版信息

Appl Microbiol Biotechnol. 2014 Apr;98(8):3529-38. doi: 10.1007/s00253-013-5485-6. Epub 2014 Jan 12.

DOI:10.1007/s00253-013-5485-6
PMID:24413974
Abstract

Canine parvovirus disease is an acute infectious disease caused by canine parvovirus (CPV). Current commercial vaccines are mainly attenuated and inactivated; as such, problems concerning safety may occur. To resolve this problem, researchers developed virus-like particles (VLPs) as biological nanoparticles resembling natural virions and showing high bio-safety. This property allows the use of VLPs for vaccine development and mechanism studies of viral infections. Tissue-specific drug delivery also employs VLPs as biological nanomaterials. Therefore, VLPs derived from CPV have a great potential in medicine and diagnostics. In this study, small ubiquitin-like modifier (SUMO) fusion motif was utilized to express a whole, naturalVP2 protein of CPV in Escherichia coli. After the cleavage of the fusion motif, the CPV VP2 protein has self-assembled into VLPs. The VLPs had a size and shape that resembled the authentic virus capsid. However, the self-assembly efficiency of VLPs can be affected by different pH levels and ionic strengths. The mice vaccinated subcutaneously with CPV VLPs and CPV-specific immune responses were compared with those immunized with the natural virus. This result showed that VLPs can effectively induce anti-CPV specific antibody and lymphocyte proliferation as a whole virus. This result further suggested that the antigen epitope of CPV was correctly present on VLPs, thereby showing the potential application of a VLP-based CPV vaccine.

摘要

犬细小病毒病是由犬细小病毒(CPV)引起的一种急性传染病。目前的商业疫苗主要是减毒活疫苗和灭活疫苗;因此,可能会出现安全性问题。为了解决这个问题,研究人员开发了病毒样颗粒(VLPs),作为类似于天然病毒体的生物纳米颗粒,具有很高的生物安全性。这种特性使得VLPs可用于疫苗开发和病毒感染机制研究。组织特异性药物递送也将VLPs用作生物纳米材料。因此,源自CPV的VLPs在医学和诊断方面具有巨大潜力。在本研究中,利用小泛素样修饰物(SUMO)融合基序在大肠杆菌中表达CPV的完整天然VP2蛋白。融合基序切割后,CPV VP2蛋白自组装成VLPs。这些VLPs的大小和形状与真实病毒衣壳相似。然而,VLPs的自组装效率会受到不同pH值和离子强度的影响。将皮下接种CPV VLPs的小鼠与接种天然病毒的小鼠的CPV特异性免疫反应进行比较。结果表明,VLPs作为完整病毒能有效诱导抗CPV特异性抗体和淋巴细胞增殖。这一结果进一步表明CPV的抗原表位正确地存在于VLPs上,从而显示了基于VLPs的CPV疫苗的潜在应用。

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