体外合成感染性RNA作为黄病毒模型中的减毒活疫苗。

In vitro-synthesized infectious RNA as an attenuated live vaccine in a flavivirus model.

作者信息

Mandl C W, Aberle J H, Aberle S W, Holzmann H, Allison S L, Heinz F X

机构信息

Institute of Virology, University of Vienna, Austria.

出版信息

Nat Med. 1998 Dec;4(12):1438-40. doi: 10.1038/4031.

DOI:10.1038/4031

PMID:9846585

Abstract

Live virus vaccines have in many cases proven to be an extremely effective tool for the prevention of viral diseases. However, the production of conventional live vaccines in eukaryotic cell cultures has many disadvantages, including the potential for contamination with adventitious agents and genetic alterations during propagation, making it necessary to do extensive testing before distribution. Based on results obtained with a flavivirus (tick-borne encephalitis virus) in an experimental animal system, we propose a novel live attenuated virus vaccination strategy consisting of the application of in vitro-synthesized infectious RNA instead of the live virus itself. When administered using the GeneGun, less than 1 ng of RNA was required to initiate replication of virus that was attenuated by a specifically engineered deletion and this induced a protective immunity in laboratory mice. Because this approach uses RNA, it does not have the potential drawbacks of DNA vaccines and thus combines the advantages of conventional live virus vaccines (for example, mimicking natural infection and inducing long-lasting immunity) with those of nucleic acid-based vaccines (for example, ease of production without a requirement for eukaryotic cell culture, stability and purity).

摘要

在许多情况下，活病毒疫苗已被证明是预防病毒性疾病的一种极其有效的工具。然而，在真核细胞培养物中生产传统的活疫苗有许多缺点，包括在繁殖过程中可能被外源因子污染以及发生基因改变，这使得在分发前必须进行广泛的测试。基于在实验动物系统中用黄病毒（蜱传脑炎病毒）获得的结果，我们提出了一种新型的减毒活病毒疫苗接种策略，即应用体外合成的感染性RNA而非活病毒本身。当使用基因枪给药时，启动经特定工程缺失减毒的病毒复制所需的RNA不到1纳克，并且这在实验室小鼠中诱导了保护性免疫。由于这种方法使用RNA，它没有DNA疫苗的潜在缺点，因此结合了传统活病毒疫苗的优点（例如，模拟自然感染并诱导持久免疫）和基于核酸的疫苗的优点（例如，易于生产，无需真核细胞培养，稳定性和纯度高）。