A Scalable, Small Molecule Enhanced High-Yield Suspension Vero Platform for VSV-Vectored Vaccine Yield to Strengthen Epidemic and Biodefence Preparedness

Vaccines based on vesicular stomatitis virus (VSV) have proven effective against deadly infections such as Ebola and represent a rapid-response platform for emerging diseases and potential biological threats. However, a major challenge remains: producing enough vaccine quickly and reliably during an outbreak or biodefence emergency. Current manufacturing methods can limit how much vaccine virus is produced, slowing response times and increasing costs. Strengthening Canada's ability to rapidly manufacture vaccines is therefore essential for epidemic preparedness and biodefence. This project aims to increase the yield of VSV-based vaccines-by 10-fold or more-using an innovative combination of biochemistry, bioprocess engineering, and artificial intelligence. We will build on a newly developed suspension version of Vero cells, a cell type widely used for vaccine manufacturing. Unlike traditional methods that require cells to grow attached to surfaces, suspension Vero cells grow freely in liquid, making production easier to scale up in bioreactors. Even in scalable systems, cells contain natural biological "brakes" that limit how efficiently vaccine viruses are produced. Instead of permanently modifying the cells through genetic engineering, we will use carefully selected small molecules that temporarily release these brakes and increase productivity. These compounds act as biochemical tools that make the same cell line more productive, enabling rapid improvements. To identify the best solutions efficiently, we will use carefully planned experiments using advanced statistical methods to test many molecules and combinations in parallel. Artificial intelligence will help prioritize the most promising candidates. We will then confirm performance and translate the approach into scalable bioreactor processes. By increasing yield and scalability, we will reduce timelines and costs while strengthening Canada's capacity for epidemic response and biodefence preparedness.