Protective immune responses induced by the immunization of mice with a recombinant bacteriophage displaying an epitope of the human respiratory syncytial virus
Protective immune responses induced by the immunization of mice with a recombinant bacteriophage displaying an epitope of the human respiratory syncytial virus
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DOI：
10.1006/viro.1997.8632
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发表时间：
1997-07-21
期刊：
影响因子：
3.7
通讯作者：
Simard, C
中科院分区：
文献类型：
--
作者：
Bastien, N;Trudel, M;Simard, C
我们调查了显示疾病特异性保护表位的重组噬菌体是否可以实验用于疫苗，以保护免疫动物免受感染。我们对重组噬菌体Fd进行了基因工程，在其表面展示了一个与人类呼吸道合胞病毒(RSV)糖蛋白G的保护性表位173-187融合的嵌合药丸外壳蛋白。一种精选的重组Fd噬菌体在小鼠中引起了强烈的免疫反应，诱导了高水平的RSV特异性抗体循环，用该重组噬菌体免疫的小鼠获得了对RSV感染的完全抵抗力，这证明了在活体RSV鼻腔攻击后，小鼠的肺中缺乏可检测到的病毒颗粒。相比之下，无论是用野生型Fd噬菌体免疫的动物还是未免疫的小鼠，肺中都发现了高水平的病毒颗粒。据我们所知，这是第一个报道噬菌体呈现免疫原肽来预防病原体感染免疫动物的能力的研究。这一发现应该有助于从随机噬菌体多肽库中选择病原体特异性保护表位的鉴定，因为它比传统的合成和偶联噬菌体特异性多肽配基序列用于免疫的方法更简单、更便宜。(C)1997年学术出版社。
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 pill 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. (C) 1997 Academic Press.