Development of a post-exposure vaccine for smallpox

据报道，在接触天花后最多四天接种疫苗可提供预防作用，尽管这种效果没有很好的文献记载。我们已经开发了一个小鼠模型系统来评估暴露于天花后潜在的预防疫苗。在这个模型中，我们展示了几种高度减毒的痘苗病毒变异株在暴露于致死剂量的wt痘苗病毒后一天鼻腔给药时可以保护病毒。在这项申请中提出的研究中，我们将评估许多痘苗病毒株在暴露后给予保护的能力。优化给药途径和剂量。对于最有希望的菌株，将确定其作用机制，并将在小鼠身上测试其对外翻病的疗效，并在沙鼠身上测试其对猴痘的疗效，为满足FDA的动物功效规则做准备。这项工作将为临床前提供 一种暴露于天花的新的暴露后预防药物的IND申请数据。

Vaccination has been reported to provide prophylaxis when administered up to four days post-exposure to smallpox, although this effect is not well documented. We have developed a mouse model system to evaluate potential vaccines for prophylaxis after exposure to smallpox. In this model we show that several highly attenuated mutant strains of vaccinia virus can protect when administered intra-nasally one day postexposure to a lethal dose of wt vaccinia virus. In the research proposed in this application we will evaluate numerous strains of vaccinia virus for their ability to protect when administered post-exposure. Route of administration and dose will be optimized. For the most promising strains, mechanism of action will be determined and efficacy will be tested in mice against ectormelia, and in ground squirrels against monkeypox, in preparation for meeting the FDA Animal Efficacy Rule. This work will provide the pre-clinical data for filing an IND fora new post-exposure prophylactic drug for exposure to smallpox.