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改良安卡拉痘苗病毒:固有免疫激活和细胞信号诱导。

Modified Vaccinia virus Ankara: innate immune activation and induction of cellular signalling.

机构信息

Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-University München, Veterinärstr. 13, 80539 Munich, Germany.

出版信息

Vaccine. 2013 Sep 6;31(39):4231-4. doi: 10.1016/j.vaccine.2013.03.017. Epub 2013 Mar 21.

DOI:10.1016/j.vaccine.2013.03.017
PMID:23523404
Abstract

Attenuated poxviruses are currently under development as vaccine vectors against a number of diseases including, influenza, HIV, malaria and tuberculosis. Modified Vaccinia virus Ankara (MVA) is an attenuated, replication deficient vaccinia virus (VACV) strain which, similar to replication competent VACV, is highly immunogenic. The lack of productive viral replication further improves the safety profile of MVA as a vector, minimizing the potential for reversion to virulent forms particularly if used in immunocompromised individuals. Despite its inability to replicate in most mammalian cells, MVA still efficiently expresses viral and recombinant genes making it a potent antigen delivery platform. Moreover, due to the loss of various immunomodulatory factors MVA infection leads to rapid local immune responses, fulfilling a requirement of an adjuvant. In this review we take a look at the immunostimulatory properties of MVA, paying particular attention to the signalling of the innate immune system in response to MVA and VACV infection. Understanding the cellular and molecular mechanisms modulated by VACV will help in the future design and engineering of new vaccines and may provide insight into previously unknown mechanisms of dominant virus-host interactions.

摘要

减毒痘病毒目前正在开发中,作为针对多种疾病的疫苗载体,包括流感、HIV、疟疾和结核病。改良安卡拉痘苗病毒(MVA)是一种减毒、复制缺陷的痘苗病毒(VACV)株,与具有复制能力的 VACV 相似,具有高度的免疫原性。缺乏有复制能力的病毒复制进一步提高了 MVA 作为载体的安全性,最大限度地降低了回复为毒力形式的可能性,特别是在免疫功能低下的个体中使用时。尽管 MVA 不能在大多数哺乳动物细胞中复制,但它仍然能够有效地表达病毒和重组基因,使其成为一种有效的抗原传递平台。此外,由于各种免疫调节因子的丧失,MVA 感染导致快速的局部免疫反应,满足了佐剂的要求。在这篇综述中,我们研究了 MVA 的免疫刺激特性,特别关注 MVA 和 VACV 感染对先天免疫系统的信号转导。了解 VACV 调节的细胞和分子机制将有助于未来新型疫苗的设计和工程,并可能为以前未知的主要病毒-宿主相互作用机制提供启示。

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