B.abortus-based vaccine against viral hemorrhagic fevers

基于流产双歧杆菌的病毒性出血热疫苗

• 批准号: 6682230
• 负责人: Ramesh Vemulapalli
• 金额: $ 26.6万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682230
• 关键词: Brucella abortus; Ebola virus; Lassa virus; active immunization; bioterrorism /chemical warfare; drug delivery systems; genetic strain; glycoproteins; laboratory mouse; nucleoproteins; recombinant DNA; transfection /expression vector; vaccine development; vector vaccine; viral vaccines; virus protein; Brucella abortus; Ebola virus; Lassa virus; active immunization; bioterrorism /chemical warfare; drug delivery systems; genetic strain; glycoproteins; laboratory mouse; nucleoproteins; recombinant DNA; transfection /expression vector; vaccine development; vector vaccine; viral vaccines; virus protein

DESCRIPTION (provided by applicant): Viral hemorrhagic fevers (VHF) are severe and life-threatening diseases caused by several viruses. Lassa virus, Crimean/Congo hemorrhagic fever virus, Marburg and Ebola viruses are four of the VHF causing agents known to be readily capable of person-to-person spread. No vaccines against these viral diseases are currently available. With the recent heightened bioterror threat, the potential use of these deadly viruses by terrorist elements has become apparent. Moreover, availability of safe and effective vaccines against VHF agents will be useful for protecting people with high risk of getting exposed to these viruses, such as people traveling to or living in the endemic regions of Africa. Research conducted to date demonstrates that both antibody and cell-mediated immune responses are necessary for protection to VHFs. The overall objective of the proposed research project is to develop a highly efficacious and safe vaccine for VHF. Specifically, the investigators propose to prepare an effective vaccine against VHF by expressing previously identified protective protein(s) of Ebola and Lassa viruses in Brucella abortus strain RB51, a bacterial vector with unique adjuvant properties and can stimulate a strong cell-mediated immune response. In the current proposal, the investigators intend to i) construct recombinant RB51 strains that express nucleoprotein and partial glycoprotein of Lassa and Ebola viruses, and ii) immunize mice with irradiated recombinant RB51 vaccines and characterize their antigen-specific antibody and cell-mediated immune responses. Recent research conducted by the investigators indicate that recombinant RB51 strains exposed to low doses of gamma radiation are unable to replicate but induce strong immune responses after just one immunization. Therefore, the investigators propose to use irradiated recombinant RB51 strains to immunize mice parentally and mucosally and study the specific immune responses. The proposed studies will clearly demonstrate the proof-of-concept for the development of efficacious and safe vaccines against viral diseases using irradiated, recombinant RB51 strain as a novel expression and delivery platform.

描述（由申请人提供）：病毒出血性发烧（VHF）是严重的，威胁生命的疾病是由多种病毒引起的。 LASSA病毒，克里米亚/刚果出血性发烧病毒，马堡和埃博拉病毒是VHF的四种，引起了人们很容易被人与人散布的剂。目前没有针对这些病毒疾病的疫苗。随着近期生物侵蚀威胁的越来越高，恐怖分子对这些致命病毒的潜在使用变得显而易见。此外，针对VHF特工的安全有效疫苗的可用性将有助于保护患有这些病毒的高风险，例如前往非洲地方性地区的人们或生活。迄今为止进行的研究表明，抗体和细胞介导的免疫反应对于对VHF的保护都是必要的。拟议的研究项目的总体目标是为VHF开发高效且安全的疫苗。具体而言，研究人员建议通过表达先前鉴定出的埃博拉病毒和LASSA病毒的保护性蛋白RB51（一种具有独特的辅助特性的细菌载体，可以刺激强细胞介导的免疫反应）来制备针对VHF的有效疫苗。在当前的建议中，研究人员打算i）构建重组RB51菌株，这些菌株表达LASSA和埃博拉病毒的核蛋白和部分糖蛋白，以及II）II）II）用辐照的重组RB51疫苗免疫小鼠，并表征其抗原特异性抗体抗体和细胞介导的免疫反应。研究人员进行的最新研究表明，暴露于低剂量的伽马辐射的重组RB51菌株无法复制，但仅一次免疫后会诱导强烈的免疫反应。 因此，研究人员建议使用辐照的重组RB51菌株对小鼠进行肠胃和粘膜免疫，并研究特定的免疫反应。拟议的研究将清楚地证明，使用辐照的，重组的RB51菌株作为一种新型表达和递送平台开发有效且安全的疫苗针对病毒疾病的概念证明。