Recombinant raccoon pox vaccine protects mice against lethal plague
Recombinant raccoon pox vaccine protects mice against lethal plague
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DOI：
10.1016/s0264-410x(02)00557-1
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发表时间：
2003-03-07
期刊：
影响因子：
5.5
通讯作者：
Stinchcomb, DT
中科院分区：
文献类型：
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作者：
Osorio, JE;Powell, TD;Stinchcomb, DT
利用浣熊痘病毒（RCN）表达系统，我们已经开发了新的重组疫苗，可以保护小鼠免受致命的鼠疫感染。我们测试了翻译增强子（EMCV-IRES）结合分泌（tPA）信号或分泌（tPA）和膜锚定（CHV-gG）信号对组织培养物中F1抗原的体外抗原表达以及诱导抗体应答和保护小鼠免受鼠疫耶尔森氏菌攻击的影响。RCN载体成功表达了Y.体外培养鼠疫菌此外，通过插入EMCV-IRES以及其与分泌信号或分泌和锚定信号的组合，表达水平增加。这些重组病毒产生保护性免疫应答，导致80%的接种小鼠在用Y.鼠疫在我们测试的基于RCN的疫苗中，RCN-IRES-tPA-YpF 1重组构建体是最有效的。用该构建体接种的小鼠经受住了多达150万个菌落形成单位的Y。鼠疫菌（7.7 x 10（4）LD 50）。有趣的是，用与锚定信号融合的F1（RCN-IR-ES-tPA-YpF 1-gG）接种引起显著的抗F1抗体滴度，但未能保护小鼠免受鼠疫攻击。我们的研究表明，在体外和体内，EMCV-IRES和分泌信号在疫苗设计中的潜在重要性。这些分子工具为提高疫苗效力提供了新的途径。此外，这些新的重组疫苗可用于人类、兽医和野生动物预防鼠疫。(C)2002爱思唯尔科技有限公司版权所有。
Using a raccoon poxvirus (RCN) expression system, we have developed new recombinant vaccines that can protect mice against lethal plague infection. We tested the effects of a translation enhancer (EMCV-IRES) in combination with a secretory (tPA) signal or secretory (tPA) and membrane anchoring (CHV-gG) signals on in vitro antigen expression of F1 antigen in tissue culture and the induction of antibody responses and protection against Yersinia pestis challenge in mice. The RCN vector successfully expressed the F1 protein of Y. pestis in vitro. In addition, the level of expression was increased by the insertion of the EMCV-IRES and combinations of this and the secretory signal or secretory and anchoring signals. These recombinant viruses generated protective immune responses that resulted in survival of 80% of vaccinated mice upon challenge with Y. pestis. Of the RCN-based vaccines we tested, the RCN-IRES-tPA-YpF1 recombinant construct was the most efficacious. Mice vaccinated with this construct withstood challenge with as many as 1.5 million colony forming units of Y. pestis (7.7 x 10(4) LD50). Interestingly, vaccination with F1 fused to the anchoring signal (RCN-IR-ES-tPA-YpF1-gG) elicited significant anti-F1 antibody titers, but failed to protect mice from plague challenge. Our studies demonstrate, in vitro and in vivo, the potential importance of the EMCV-IRES and secretory signals in vaccine design. These molecular tools provide a new approach for improving the efficacy of vaccines. In addition, these novel recombinant vaccines could have human, veterinary, and wildlife applications in the prevention of plague. (C) 2002 Elsevier Science Ltd. All rights reserved.