Development of a New Tularemia Vaccine

新型兔热病疫苗的开发

• 批准号: 7093546
• 负责人: MINGTAO ZENG
• 金额: $ 30.47万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093546
• 关键词: Adenoviridae; Francisella tularensis; bacterial proteins; bacterial vaccines; bioterrorism /chemical warfare; drug administration routes; immune response; laboratory mouse; mucosal immunity; tularemia; vaccine development; vaccine evaluation; vector vaccine

DESCRIPTION (provided by applicant): Tularemia is a zoonotic disease caused by the highly virulent, facultative intracellular bacterium Francisella tularensis. Because of the virulence of this bacterium and its ease of aerosol transmission, it has been classified as a Category A bioterrorism agent. A live, attenuated tularemia vaccine containing F. tularensis LVS (live vaccine strain) is currently available for human use as an investigational new drug (IND). It is given by scarification; this delivery method is sub-optimal for rapid, mass vaccination and the product has reactogenicity issues. Therefore, an improved vaccine against tularemia is needed. The objective of this research is to develop an effective and easily administrated tularemia vaccine using four protein antigens: Tul4, FopA, Cpn60 (heat shock protein), and FT23KDAP (the 23 kDa protein) from F. tularensis as vaccine components, delivered with replication-defective adenovirus by the intranasal and transcutaneous immunization routes. These non-invasive vaccine delivery methods will undoubtedly enhance the compliance of a vaccination program. In this project, adenovirus and plasmid expression vectors encoding Tul4, FopA, Cpn60, and FT23KDAP will be constructed. In order to obtain an optimal vaccination protocol, immunization regimens with different combinations of adenovirus and plasmid vectors and with different sequences of intranasal, transcutaneous, and intramuscular delivery modes will be studied in a mouse model. The specific aims of this project are: Specific Aim #1: To develop a replication-defective, adenovirus-vectored vaccine against F. tularensis. Specific Aim #2: To compare the systemic and mucosal immunity elicited by the adenovirus-vectored vaccine delivered by combinations of intranasal, transcutaneous, and intramuscular administrations with that elicited by F. tularensis LVS through intradermal injection. Since no previous research has shown that genetic immunization with adenovirus or plasmid vectors could elicit protective immunity to F. tularensis, the proposed project is exploratory and developmental in nature.

描述（由申请人提供）： 兔热病是一种人畜共患疾病，由高毒力、兼性细胞内细菌土拉弗朗西斯菌引起。由于这种细菌的毒力及其易于气溶胶传播，它被归类为 A 类生物恐怖主义制剂。含有土拉菌 LVS（活疫苗株）的土拉菌活减毒疫苗目前可作为研究性新药 (IND) 供人类使用。它是通过划痕获得的；这种递送方法对于快速、大规模疫苗接种来说不是最佳选择，并且该产品存在反应原性问题。因此，需要一种针对兔热病的改进疫苗。本研究的目的是开发一种有效且易于施用的兔热病疫苗，使用四种蛋白抗原：Tul4、FopA、Cpn60（热休克蛋白）和来自土拉热兔的 FT23KDAP（23 kDa 蛋白）作为疫苗成分，并通过复制传递-通过鼻内和经皮免疫途径的缺陷型腺病毒。这些非侵入性疫苗接种方法无疑将提高疫苗接种计划的合规性。在该项目中，将构建编码Tul4、FopA、Cpn60和FT23KDAP的腺病毒和质粒表达载体。为了获得最佳的疫苗接种方案，将在小鼠模型中研究腺病毒和质粒载体的不同组合以及鼻内、经皮和肌内递送模式的不同序列的免疫方案。 该项目的具体目标是： 具体目标#1：开发一种针对土拉弗朗西斯菌的复制缺陷型腺病毒载体疫苗。 具体目标#2：比较通过鼻内、经皮和肌内注射联合给药的腺病毒载体疫苗引起的全身和粘膜免疫与土拉弗朗西斯菌LVS通过皮内注射引起的全身和粘膜免疫。 由于之前没有研究表明腺病毒或质粒载体的基因免疫可以引发对土拉弗朗西斯菌的保护性免疫，因此拟议的项目本质上是探索性和开发性的。