(497b) Mechanistic Modeling of Sars-Cov-2 Virus-like Particle (VLP) Vaccine Production

The COVID-19 pandemic has highlighted the need for effective and scalable vaccine technologies that can be tuned to rapidly mutating contagions. Virus-like particles (VLPs) are a promising vaccine platform because they are highly immunogenic, innately multi-antigenic, and safe. However, mammalian VLP manufacturing processes are not currently capable of meeting worldwide vaccination demand. To address this need, we developed mechanistic models of the SARS-CoV-2 VLP production process to support improvements to productivity and product quality. First, we developed a mechanistic model of SARS-CoV-2 VLP production at the cellular scale that mathematically describes the intracellular steps (e.g., transcription, translation, transport, assembly, and secretion), empowering the identification of inefficiencies that can be remedied through targeted cell line engineering and operational adjustments. We then extended the intracellular model to the bioreactor scale to understand how process inputs affect cellular outputs such as productivity and product quality. These mechanistic models enable rapid process development and improved process control, which will ultimately reduce the time to rollout of VLP vaccines.