Nodaviral RNA vaccine vector amplified in yeast

在酵母中扩增的 Nodavir RNA 疫苗载体

• 批准号: 6654460
• 负责人: L A BALL
• 金额: $ 14.5万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6654460
• 关键词: RNA virus; Saccharomyces cerevisiae; cell mediated lymphocytolysis test; cellular immunity; enzyme linked immunosorbent assay; gag protein; human immunodeficiency virus; humoral immunity; immunization; intramuscular injections; laboratory mouse; northern blottings; nucleic acid amplification techniques; replicon; tissue /cell culture; transfection; vaccine development; vector vaccine; virus protein; western blottings

DESCRIPTION (provided by applicant): Human Immunodeficiency Virus (HIV) is a global health threat, likely to be controlled only by the development of an easily manufactured vaccine capable of eliciting strong humoral and cellular immune responses. Nodamura virus (NoV), a small positive-sense RNA virus, has many advantages for development as live vector vaccines, which are safer than attenuated or inactivated HIV vaccines, yet can elicit humoral and cellular immunity. As described in this proposal, NoV replicates to nearly the level of rRNA in the yeast S. cerevisiae, providing an inexpensive supply of RNA. A decade of hepatitis B vaccine production in yeast demonstrates the safety and cost-effectiveness of this organism. Recently, intramuscular immunization with in vitro transcribed recombinant Semliki Forest virus-derived naked RNA replicons has been shown to elicit significant levels of protection in mouse models of three economically important viruses. The goal of this pilot project is to develop an HIV vaccine based on a NoV RNA-derived, suicidal vector encoding HIV proteins. The novel feature of this proposal is that the RNA will be amplified in the yeast S. cerevisiae and introduced into mammals as naked RNA in yeast total RNA.We propose to do this by addressing the following specific aims: 1. To determine the immunologic effects of immunizing mice with yeast total RNA. 2. To characterize the replication and expression of viral RNA vectors encoding HIV genes in tissueculture. 3. To determine immunization routes, schedules, and viral RNA vector formulations that induce significant immune responses to HIV gene products in mice.

描述（由申请方提供）：人类免疫缺陷病毒（HIV）是一种全球性健康威胁，可能只能通过开发一种能够引发强烈体液和细胞免疫应答的易于制造的疫苗来控制。 野田村病毒（Nodamura virus，NoV）是一种小的正义RNA病毒，具有比减毒或灭活HIV疫苗更安全、更能诱导体液免疫和细胞免疫等优点，是一种新型的HIV活载体疫苗。 如该提案中所述，NoV复制到接近酵母S中rRNA的水平。酿酒酵母，提供廉价的RNA供应。 十年来在酵母中生产B型肝炎疫苗证明了这种生物的安全性和成本效益。 最近，肌内免疫与体外转录的重组Semliki森林病毒衍生的裸RNA复制子已被证明引发显着水平的保护在小鼠模型中的三个经济上重要的病毒。 该试点项目的目标是开发一种基于编码HIV蛋白的NoV RNA衍生的自杀性载体的HIV疫苗。 该方案的新特点是RNA将在酵母S.酿酒酵母和引入哺乳动物作为裸RNA在酵母总RNA。我们建议这样做，解决以下具体目标：1。 探讨酵母总RNA免疫小鼠的免疫效果。 2. 目的研究编码HIV基因的病毒RNA载体在组织培养中的复制和表达。 3. 确定在小鼠中诱导对HIV基因产物的显著免疫应答的免疫途径、时间表和病毒RNA载体制剂。