Grant: Collaborative Health Research Projects

Virus-based vaccines are society's most successful pharmaceuticals for the prevention of deadly human diseases. Diseases like smallpox, polio, measles, mumps and rubella have been essentially eliminated from human populations where widespread vaccination programs have been implemented. One characteristic common to all vaccines is that they must be engineered or selected to have attenuated growth characteristics in order to ensure an acceptable safety profile in humans. While attenuation of the ability of a viral vaccine to block cellular innate immune responses creates an extremely safe product, it also impairs the growth of the virus in cell lines used for industrial manufacturing, decreasing the timely delivery of vaccines. The acute vaccine supply shortages experienced during the 2009 H1N1 vaccination program underscore the need fortimely manufacturing of large amounts of vaccine. Our Solution: We have discovered that it is possible to use small molecules to target and inhibit the same cellular pathways that virus virulence genes target. Our lead compounds, coined virus sensitizers or VSes, can significantly enhance the growth of viral therapeutics, in some cases by over 1000 fold. A key advantage of using small molecules to boost vaccine production is that neither the virus-based vaccine nor the manufacturingcell line need be genetically modified. This minimizes the regulatory hurdles for implementing our technology to improving vaccine manufacturing, enabling faster translation to improved health outcomes for Canadians. To translate our technology to an industrial setting, several key issues need to be addressed. These include (1) Optimization of VSe activity and physiocochemical properties (2) Assessment of VSe toxicology and end-product bioequivalence (3) Validation of VSe impact in small scale manufacturing applications, which will be done in collaboration with our technology end user Jennerex Biotherapeutics, and (4) Identification of VSe molecular targets. This proposal describes our multi-disciplinary approach to address these key questions.