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两种广泛特异性的重组单价 llama 来源抗体片段在体外中和轮状病毒感染。

In vitro neutralisation of rotavirus infection by two broadly specific recombinant monovalent llama-derived antibody fragments.

机构信息

Enteric Virus Unit, Centre for Infections, Health Protection Agency, London, United Kingdom.

出版信息

PLoS One. 2012;7(3):e32949. doi: 10.1371/journal.pone.0032949. Epub 2012 Mar 5.

DOI:10.1371/journal.pone.0032949
PMID:22403728
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3293919/
Abstract

Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains.

摘要

轮状病毒是导致婴幼儿病毒性肠胃炎的主要原因。因此,开发廉价的抗病毒产品来预防和/或治疗轮状病毒病仍然是当务之急。此前,我们已经表明,一种源自感染轮状病毒的骆驼重链抗体的单价重组抗体片段(称为抗轮状病毒蛋白或 ARP1)能够在小鼠模型系统中中和轮状病毒感染。在本工作中,我们研究了两种骆驼抗体片段 ARP1 和 ARP3 对 13 种不同基因型的细胞培养适应型轮状病毒株的特异性和中和活性。此外,还进行了免疫捕获电子显微镜(IEM)以确定 ARP1 与临床分离株和细胞培养适应株的结合。ARP1 和 ARP3 能够在体外中和多种轮状病毒血清型/基因型,此外,IEM 还显示出与多种细胞适应株以及来自临床标本的株的特异性结合。这些结果表明,这些分子有可能作为预防和/或治疗广泛临床相关轮状病毒株感染的免疫预防和/或免疫治疗产品。

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2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis.2008 年全球轮状病毒相关死亡率估计:在普遍轮状病毒疫苗接种计划推出之前,5 岁以下儿童:系统评价和荟萃分析。
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Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG).轮状病毒分类工作组(RCWG)建议的轮状病毒毒株命名统一。
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单域抗体及其对抗病毒感染的改造
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Structural Basis of Nanobodies Targeting the Prototype Norovirus.针对原型诺如病毒的纳米抗体的结构基础。
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Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future.针对诺如病毒和轮状病毒的治疗与免疫预防:过去、现在与未来
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Anti-VP6 VHH: An Experimental Treatment for Rotavirus A-Associated Disease.抗-VP6 VHH:一种针对A组轮状病毒相关疾病的实验性治疗方法。
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