MagaVax vaccine for Ebola

埃博拉病毒(EBOV)是一种可怕的病毒，它定期从动物储藏室出现，导致严重和 致命的流行病。一种新开发的复制型病毒疫苗(rVSV-ZEBOV)被成功地用于 暴露后疫苗，用于暴露后的高危人群。然而，这种抗体诱导疫苗 已在许多健康受试者中引起发烧和关节炎，因此不宜作为预防药物服用 疫苗。相反，研发一种能产生保护性CD8+T细胞反应的疫苗的工作仍在继续 抗埃博拉糖蛋白(GP)蛋白。不幸的是，目前开发的以腺病毒为基础的 基于MVA的疫苗在人类中引起次优的CD8+T细胞反应。因此，该项目将 开发一种基于GP抗原与高效、多三聚体CD40相结合的新疫苗 配体(CD40L或CD154)。疫苗的设计是基于一种由表面活性物质主体组成的融合蛋白。 蛋白D(Spd)作为多聚体支架与GP和CD40L胞外区的结合 (SPD-GP-CD40L)。这被称为多三聚体抗原佐剂疫苗或“MagaVax”。我们的目标是 为了将其构建在腺病毒载体中，测试其在小鼠体内诱导抗GP CD8+T细胞的有效性 活体，并准备一个猕猴版本，以供最终在猴子身上测试。当这些研究完成后，一个 MagaVax/EBOV疫苗将准备好进一步测试和开发，以对抗埃博拉病毒。

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.