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.
Ebola virus infection is a current threat that recently infected over 28,000 people in West Africa and was then carried by exposed individuals into the United States. This project will develop a strong preventative vaccine against Ebola that works by eliciting T cells to clear this virus from the body.
