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抗独特型疫苗接种预防小鼠冠状病毒感染。

Antiidiotypic vaccination against murine coronavirus infection.

作者信息

Lamarre A, Lecomte J, Talbot P J

机构信息

Virology Research Center, Université du Québec, Laval, Canada.

出版信息

J Immunol. 1991 Dec 15;147(12):4256-62.

PMID:1661313
Abstract

Rabbit polyclonal antiidiotypic antibodies were generated against a neutralizing mAb specific for a conformational epitope on the S glycoprotein of murine hepatitis virus, strain A59 (MHV-A59). These anti-Id were directed predominantly against an Id that was undetectable in rabbit and rat anti-MHV-A59 sera and weakly represented in syngeneic and allogeneic antiviral sera. However, some partial idiotypic sharing was observed between the Id-bearing antibody and a mAb with a similar antigenic site specificity. The anti-Id inhibited the virus-binding and neutralizing activities of the immunizing antibody, demonstrating that they recognize paratope-associated idiotopes. Mice immunized with affinity-purified anti-Id developed MHV-A59-specific antibodies that neutralized viral infectivity to high titers. Moreover, these animals survived an otherwise lethal challenge with viral murine hepatitis virus, unlike control mice immunized with normal rabbit Ig. These results indicate that at least a subpopulation of the polyclonal anti-Id could induce a protective immune response directed toward a biologically important MHV-A59 epitope, and demonstrate the feasibility of antiidiotypic vaccination against a coronavirus infection.

摘要

针对鼠肝炎病毒A59株(MHV - A59)S糖蛋白上构象表位的一种中和单克隆抗体(mAb),制备了兔多克隆抗独特型抗体。这些抗独特型抗体主要针对一种独特型,该独特型在兔和大鼠抗MHV - A59血清中无法检测到,在同基因和异基因抗病毒血清中也仅有微弱表达。然而,在携带独特型的抗体与具有相似抗原位点特异性的单克隆抗体之间观察到了一些部分独特型共享现象。抗独特型抗体抑制了免疫抗体的病毒结合和中和活性,表明它们识别与互补位相关的独特型表位。用亲和纯化的抗独特型抗体免疫的小鼠产生了MHV - A59特异性抗体,这些抗体能高效中和病毒感染性。此外,与用正常兔免疫球蛋白免疫的对照小鼠不同,这些动物在受到致死剂量的鼠肝炎病毒攻击后存活了下来。这些结果表明,至少多克隆抗独特型抗体的一个亚群能够诱导针对生物学上重要的MHV - A59表位的保护性免疫反应,并证明了抗独特型疫苗接种针对冠状病毒感染的可行性。

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