Development of a post-exposure vaccine for smallpox

天花暴露后疫苗的开发

• 批准号: 6998645
• 负责人: Bertram L. Jacobs
• 金额: $ 109.74万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998645
• 关键词: Poxviridae; Poxviridae disease; disease /disorder model; drug administration rate /duration; drug screening /evaluation; genetic strain; genetically modified animals; immune response; inhalation drug administration; laboratory mouse; nonhuman therapy evaluation; pharmacokinetics; plaque assay; polymerase chain reaction; smallpox vaccine; squirrel; vaccine development; vaccine evaluation; vaccinia virus

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.

据报道，在接触天花后4天内接种疫苗可提供预防作用，尽管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，我们展示了几种高度减毒的突变株痘苗病毒，当暴露于致命剂量的wt痘苗病毒后一天鼻内给予时，可以保护。在本申请中提出的研究中，我们将评估多种牛痘病毒株在暴露后接种时的保护能力。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，并在小鼠和地松鼠身上测试其抗湿疹和猴痘的功效，为满足FDA动物功效规则做准备。这项工作将提供临床前