Design of formulation processes for improved thermostability of viral vaccines

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Viral vectored vaccines are among the most advanced vaccine candidates currently evaluated in COVID-19 phase-3 clinical trials. Following their manufacturing, thermostability is a critical quality attribute to ensure the efficacy and safe delivery of these life-saving products where needed. Building on an extensive scientific knowledge and know-how of cell-culture produced viruses, we propose for this research program to direct our efforts to study and integrate in the process development cycle, liquid and solid formulations of viral vaccines, an area of process development that remained largely empirical. As a result, a novel hybrid model will enable the freeze-dryer optimal operations in real-time. The long-term objective of this research program is to identify the critical parameters and uncover their mechanisms of action towards integration of expert knowledge for digitally assisted design of liquid and solid formulations of effective viral vaccines with improved thermostability and cost-effectiveness. We aim to 1) Design enhanced liquid formulations and uncover mechanisms involved in the formulation of enveloped viruses such as Vesicular Stomatitis Virus (VSV) and lentivirus in presence of excipients to preserve their biological activity; 2) Design solid formulations and develop mechanistic model for freeze-drying of enveloped and non-enveloped viruses such as VSV and adenovirus vectored vaccines generating a large pool of quality data for Machin Learning; 3) Develop a Hybrid model for freeze-drying process using a digital twin approach by combining mechanistic and data-driven models. The digital twin is connected to the physical freeze-dryer by sensors and feed-back control to accelerate the design and optimal operation of freeze-drying processes of viral vaccines. In collaboration with experts in the field (co-supervisors from McGill), we propose to combine recent advancements in Machine Learning (ML) algorithms to assist the design of experiments and accelerate the design of robust vaccine formulations and processes. Experimentation, validation of results and digital twin-based optimization of freeze-drying process will be executed in our already functional biosafety level-2+ laboratory and supported by our validated process analytical technologies. This research will advance knowledge on formulation of enveloped and non-enveloped viruses leading to discovery of novel excipients and enhanced processes. By focusing the design approach on improving the thermostability of the VSV-vectored Ebola vaccine, we will facilitate the delivery and stockpiling of this life-saving product as well as other products using the same VSV delivery platform of antigens (HIV-1, SARS-CoV-2). Critically, this research program will contribute to training 16 HQPs to respond to the high demand of qualified personnel expressed by the vaccine biomanufacturing industry in Canada.