Development of a post-exposure vaccine for smallpox

据报道，在接触天花后4天内接种疫苗可提供预防，但这种效果没有很好的记录。我们已经开发了一种小鼠模型系统，以评估暴露于天花后预防的潜在疫苗。在这个模型中，我们表明，几个高度减毒的突变株的牛痘病毒可以保护时，鼻内给药后一天的致死剂量的野生型牛痘病毒。在本申请中提出的研究中，我们将评估许多牛痘病毒株在暴露后给药时的保护能力。将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，并在小鼠中检测其对鼠痘的有效性，在地松鼠中检测其对猴痘的有效性，为满足FDA动物有效性规则做准备。这项工作将提供临床前 用于申请一种新的暴露后预防天花药物的IND的数据。

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.