Development of a conditionally replicating vaccinia virus platform As an alternative to Modified Vaccinia Ankara for cancer immunotherapy and vaccine production

Supervisors: John Bell & Carolina Ilkow, uOttawa The COVID-19 pandemic demonstrated the importance of flexible, readily available, and local vaccine platforms in the event of another potential viral infection. The development of improved vaccine platforms is not only essential for the prevention of infectious diseases, but is also being considered as a potential cancer treatment. As cancer is the leading cause of death in Canada, these technologies can vastly improve the standard of care in the country and pave the way for a substantial reduction in the number of cancer-related deaths. Vaccinia Virus was used to eradicate smallpox more than a century ago, and its modern descendants have been improved for greater safety and used to develop vaccines for other infectious diseases, such as the recent outbreak of monkeypox. Nonetheless, both the large-scale production and the immune response to these vaccines have significant room for improvement. We have developed a novel platform based on the vaccinia virus to address these issues. This platform has the potential to overcome the challenges associated with the production, capacity, and stability of current vaccines, and will be engineered for higher immune activation to be administered in a single dose. First, we determined the platform's safety in immune-deficient mouse model; we did not observe any severe side effects or significant weight loss. Then, we confirmed that our platform generated high levels of SARS-CoV-2 proteins. In the next step, we will modify the platform to express antigens from multiple strains of SARS-CoV-2 to demonstrate vaccination against multiple strains. In addition, using colon cancer and skin cancer mouse models, we will evaluate the therapeutic efficacy of our platform when expressing tumor antigens. Overall, we hypothesize that our new platform can serve as a safe and effective vaccine platform for infectious diseases and cancer treatment.