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用展示人呼吸道合胞病毒表位的重组噬菌体免疫小鼠诱导的保护性免疫反应。

Protective immune responses induced by the immunization of mice with a recombinant bacteriophage displaying an epitope of the human respiratory syncytial virus.

作者信息

Bastien N, Trudel M, Simard C

机构信息

Centre de recherche en virologie, Institut Armand-Frappier, Laval des Rapides, Ville de Laval, Québec, Canada.

出版信息

Virology. 1997 Jul 21;234(1):118-22. doi: 10.1006/viro.1997.8632.

DOI:10.1006/viro.1997.8632
PMID:9234952
Abstract

We investigated whether a recombinant bacteriophage displaying a disease-specific protective epitope could be experimentally used as a vaccine to confer protection of immunized animals against infection. We genetically engineered a recombinant phage, fd, displaying at its surface a chimeric pIII coat protein fused to the previously identified protective epitope 173-187 from the glycoprotein G of the human respiratory syncytial virus (RSV). A selected recombinant fd phage elicited a strong immune response in mice, inducing a high level of circulating RSV-specific antibodies. Mice immunized with the recombinant phage acquired a complete resistance to RSV infection as evidenced by the lack of detectable virus particles in their lungs following intranasal challenge with live RSV. In contrast, a high level of virus particles was found in the lungs of either animals immunized with the wild-type fd phage or nonimmunized mice. To our knowledge, this is the first study to report the ability of a phage presenting an immunogenic peptide to prevent infection of immunized animals by a pathogen. This finding should facilitate the identification of pathogen-specific protective epitopes selected from random phage peptide libraries, as it is simpler and less expensive than the conventional method of synthesis and coupling of phage-specific peptide ligand sequences for immunization.

摘要

我们研究了展示疾病特异性保护性表位的重组噬菌体是否可作为疫苗进行实验性应用,以保护免疫动物免受感染。我们对一种重组噬菌体fd进行了基因工程改造,使其表面展示一种嵌合的pIII外壳蛋白,该蛋白与先前鉴定的来自人类呼吸道合胞病毒(RSV)糖蛋白G的保护性表位173 - 187融合。一种选定的重组fd噬菌体在小鼠体内引发了强烈的免疫反应,诱导产生了高水平的循环RSV特异性抗体。用重组噬菌体免疫的小鼠获得了对RSV感染的完全抗性,这一点通过用活RSV进行鼻内攻击后在其肺部未检测到病毒颗粒得到证明。相比之下,在用野生型fd噬菌体免疫的动物或未免疫小鼠的肺部发现了高水平的病毒颗粒。据我们所知,这是第一项报道呈现免疫原性肽的噬菌体能够预防免疫动物被病原体感染的能力的研究。这一发现应有助于从随机噬菌体肽库中鉴定病原体特异性保护性表位,因为它比用于免疫的噬菌体特异性肽配体序列的传统合成和偶联方法更简单、成本更低。

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