MagaVax vaccine for Ebola

埃博拉病毒 MagaVax 疫苗

• 批准号: 9254569
• 负责人: Richard Syd Kornbluth
• 金额: $ 22.5万
• 依托单位: MULTIMERIC BIOTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9254569
• 关键词: MagaVax; vaccine; Ebola

Ebola virus (EBOV) is a dreaded virus that periodically emerges from its animal reservoir to cause serious and deadly epidemics. A recently developed replicating viral vaccine (rVSV-ZEBOV) was successfully used as a post-exposure vaccine for persons at high risk following exposure. However, this antibody-inducing vaccine has caused fever and arthritis in many healthy subjects which makes unsuitable to give as a prophylactic vaccine. Instead, work continues on developing a vaccine that generates protective CD8+ T cell responses against the Ebola glycoprotein (GP) protein. Unfortunately, the currently developed Adenoviral-based and MVA-based vaccines elicit a suboptimal CD8+ T cell response in humans. Consequently, this project will develop a new vaccine based on combining GP antigen with a highly effective, multi-trimer form of CD40 ligand (CD40L or CD154). The vaccine design is based on a fusion protein comprised of the body of surfactant protein D (SPD) as a multimerization scaffold (SPD) combined with GP and the extracellular domain of CD40L (SPD-GP-CD40L). This is referred to as a Multi-Trimer Antigen Adjuvant Vaccine or “MagaVax.” The Aims are to make the construct in an adenoviral vector, test its effectiveness at eliciting anti-GP CD8+ T cells in mice in vivo, and prepare a macaque version for eventual testing in monkeys. When these studies are complete, a MagaVax/EBOV vaccine will be ready for further testing and development as defense against Ebola.

埃博拉病毒（EBOV）是一种可怕的病毒，从其动物储层中定期出现以引起严重和 致命的流行病。最近开发的复制病毒疫苗（RVSV-ZEBOV）成功用作 暴露后风险高风险的人的暴露后疫苗。但是，这种抗体诱导的疫苗 在许多健康受试者中引起了发烧和关节炎，这使得不适合作为预防性 疫苗。相反，继续开发产生保护性CD8+ T细胞反应的疫苗的工作 针对埃博拉糖蛋白（GP）蛋白。不幸的是，目前开发的基于腺病毒的和 基于MVA的疫苗会引起人类的次优CD8+ T细胞反应。因此，这个项目将 开发一种基于将GP抗原与高效的多用途CD40组合的新疫苗 配体（CD40L或CD154）。疫苗设计基于由表面活性剂体组成的融合蛋白 蛋白D（SPD）作为多层化支架（SPD）与GP结合使用CD40L的细胞外域 （SPD-GP-CD40L）。这被称为多三位体抗原辅助疫苗或“ magavax”。目的是 要使腺病毒载体中的构建体测试其在诱导小鼠抗GP CD8+ T细胞中的有效性 Vivo，准备猕猴的猕猴版本。这些研究完成后， Magavax/EBOV疫苗将准备进一步测试和开发作为对埃博拉病毒的防御。