MagaVax vaccine for Ebola

埃博拉病毒（EBOV）是一种可怕的病毒，定期从其动物宿主中出现，导致严重和 致命的流行病最近开发的复制型病毒疫苗（rVSV-ZEBOV）成功地用作疫苗。 为暴露后高危人群接种暴露后疫苗。然而，这种抗体诱导疫苗 在许多健康的受试者中引起发烧和关节炎，这使得不适合作为预防剂给予 疫苗相反，开发一种能产生保护性CD 8 + T细胞应答的疫苗的工作仍在继续。 埃博拉病毒糖蛋白（GP）蛋白。不幸的是，目前开发的基于腺病毒和 基于MVA的疫苗在人体中引发次优的CD 8 + T细胞应答。因此，该项目将 开发一种基于GP抗原与高效的多三聚体形式的CD 40相结合的新疫苗 配体（CD 40 L或CD 154）。疫苗设计是基于融合蛋白组成的身体表面活性剂 蛋白D（SPD）作为多聚化支架（SPD）与GP和CD 40 L的胞外结构域结合 （SPD-GP-CD40L）。这被称为多三聚体抗原佐剂疫苗或“MagaVax”。其宗旨是 为了在腺病毒载体中制备该构建体，测试其在小鼠中诱导抗GP CD 8 + T细胞的有效性， 体内，并准备一个猕猴版本的最终测试猴子。当这些研究完成后， MagaVax/EBOV疫苗将准备进一步测试和开发，以抵御埃博拉病毒。

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.