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一种临床批准的新型麻疹病毒疫苗载体的序列和免疫原性

Sequence and immunogenicity of a clinically approved novel measles virus vaccine vector.

作者信息

Zuniga Amando, Liniger Mathias, Morin Teldja Neige Azzouz, Marty René R, Wiegand Marian, Ilter Orhan, Weibel Sara, Billeter Martin A, Knuchel Marlyse C, Naim Hussein Y

机构信息

Current affiliations: Zurich University of Applied Sciences; Wädenswil, Switzerland.

出版信息

Hum Vaccin Immunother. 2013 Mar;9(3):607-13. doi: 10.4161/hv.23242. Epub 2013 Jan 16.

Abstract

The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of MVb, was constructed. Phylogenic and phenotypic analysis revealed that MVbv and the rescued MVb constitute another evolutionary branch within the hitherto classified measles vaccines. Plasmid p(+)MVb was modified by insertion of artificial MV-type transcription units (ATUs) for the generation of recombinant viruses (rMVb) expressing additional proteins. Replication characteristics and immunogenicity of rMVb vectors were similar to the parental MVbv and to other vaccine strains. The expression of the additional proteins was stable over 10 serial virus transfers, which corresponds to an amplification greater than 10 ( 20) . The excellent safety record and its efficient application as aerosol may add to the usefulness of the derived vectors.

摘要

麻疹病毒疫苗(MVbv)是一种临床认证且耐受性良好的疫苗株,已通过肠胃外和黏膜途径接种。它已在儿童中广泛使用,并已证明在引发保护性免疫方面是安全有效的。因此,选择这种特定的毒株来构建麻疹病毒载体。分离并测序了商业MVbv疫苗株的基因组,并构建了一种质粒p(+)MVb,该质粒能够转录病毒抗原组并拯救MVb。系统发育和表型分析表明,MVbv和拯救出的MVb在迄今分类的麻疹疫苗中构成了另一个进化分支。通过插入人工MV型转录单元(ATUs)对质粒p(+)MVb进行修饰,以产生表达额外蛋白质的重组病毒(rMVb)。rMVb载体的复制特性和免疫原性与亲本MVbv以及其他疫苗株相似。额外蛋白质的表达在连续10次病毒传代中保持稳定,这相当于扩增超过10(20)。出色的安全记录及其作为气溶胶的高效应用可能会增加衍生载体的实用性。

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