The team working on this project believes it has developed a vaccine vector that will produce a better immune response than existing preventive therapies for a variety of hard-to-treat viruses. Genes from HIV are added to a patented, attenuated mutation of the vaccinia virus, drawing the immune system’s attention to the target virus’s proteins, thereby provoking a strong immune response.
One of the critical advantages of using vaccinia virus is its affordability: it is very cheap to culture, easy to administer (usually by scratching the skin), and doesn’t require temperature stabilization. Its relative safety for humans means that it can be used as an effective delivery system for a variety of viral antigens. In addition to HIV vaccine applications, the method is being used to develop a safer, more effective smallpox vaccine and the platform is also being applied to hepatitis B.
Current research revolves around understanding mechanisms of molecular activity in interferon, particularly as they concern control of gene expression at the level of translation. Interferons are a set of proteins secreted by vertebrate cells in response to virus infection or antigen stimulation. Interferon inhibits viral replication by inducing a double stranded RNA-activated protein kinase, PKR, which can phosphorylate, and inactivate eukaryotic protein synthesis initiation factor 2, thus preventing synthesis of viral proteins. It also acts to inhibit cell proliferation.
Numerous viruses, including vaccinia virus, have been shown to code for inhibitors of the interferon-induced protein kinase. These virus-encoded inhibitors allow the virus to circumvent one of the organism’s main defenses against virus protection and they also appear to prevent infected cells from committing suicide in response to infection. The project team aims to understand the molecular nature of the vaccinia viral kinase inhibitors and what role these inhibitors have in replication of these viruses in mammalian cells in culture and in infected animals. The goal is to use these studies in the development of safer, more effective vaccines for both humans and animals.
Each month, innovative research from the Biodesign Institute appears in the world’s premier scientific journals. Many such studies have graced the covers of these journals, showcasing Biodesign research ranging from water remediation to nanometer-scale structures built from DNA.
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