Department of Pathobiology and Veterinary Science, College of Agriculture and Natural Resources, University of Connecticut, Storrs, CT, USA.
Hum Vaccin Immunother. 2012 Jul;8(7):961-70. doi: 10.4161/hv.21080. Epub 2012 Jul 1.
In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses, including smallpox virus (variola virus). Over time, vaccinia virus (VACV) replaced cowpox virus as the smallpox vaccine, and vaccination efforts eventually led to the successful global eradication of smallpox in 1979. VACV has many characteristics that make it an excellent vaccine and that were crucial for the successful eradication of smallpox, including (1) its exceptional thermal stability (a very important but uncommon characteristic in live vaccines), (2) its ability to elicit strong humoral and cell-mediated immune responses, (3) the fact that it is easy to propagate, and (4) that it is not oncogenic, given that VACV replication occurs exclusively within the host cell cytoplasm and there is no evidence that the viral genome integrates into the host genome. Since the eradication of smallpox, VACV has experienced a renaissance of interest as a viral vector for the development of recombinant vaccines, immunotherapies, and oncolytic therapies, as well as the development of next-generation smallpox vaccines. This revival is mainly due to the successful use and extensive characterization of VACV as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector. This review provides an overview of new uses of VACV that are currently being explored for the development of vaccines, immunotherapeutics, and oncolytic virotherapies.
1796 年，爱德华·詹纳（Edward Jenner）引入了牛痘病毒（一种痘病毒科的正痘病毒）接种的概念，该病毒能引发针对相关正痘病毒（包括天花病毒）的交叉保护免疫。随着时间的推移，牛痘病毒（VACV）取代了牛痘病毒成为天花疫苗，疫苗接种工作最终导致 1979 年全球成功根除天花。VACV 具有许多使其成为优秀疫苗的特性，这些特性对成功根除天花至关重要，包括：（1）其出色的热稳定性（活疫苗中非常重要但不常见的特征）；（2）能够引发强大的体液和细胞免疫反应；（3）易于繁殖；（4）由于 VACV 复制仅发生在宿主细胞质内，并且没有证据表明病毒基因组整合到宿主基因组中，因此它不致癌。自天花根除以来，VACV 作为开发重组疫苗、免疫疗法和溶瘤疗法以及下一代天花疫苗的病毒载体，重新引起了人们的兴趣。这种复兴主要是由于 VACV 在根除天花运动中作为疫苗的成功使用和广泛特征描述，以及能够遗传操作其大型 dsDNA 基因组而保留感染性和免疫原性、广泛的哺乳动物宿主范围以及其自然对肿瘤细胞的趋向性，使其可作为溶瘤病毒载体。这篇综述概述了目前正在探索用于开发疫苗、免疫疗法和溶瘤病毒疗法的 VACV 的新用途。
