Pillar 4
Functional Genomics & Structure-Function of VOCs

Vaccines have been instrumental in our response to the COVID-19 pandemic.  At the time of publication (January 2022), more than 300 vaccine candidates had been designed, produced, and tested in animals. Among them, 21 had been approved for emergency use in humans and dozens more were in clinical trials. Continued vaccine development is important due to emergence of variants of concern (VOCs) that may escape immune responses and a growing world population that needs access to vaccine resources that are easily deployable.  Here, the researchers reported the preclinical development of a lipid nanoparticle-formulated and mRNA-based SARS-CoV-2 vaccine called PTX-COVID19-B.  PTX-COVID19-B was chosen out of three candidates after the initial intramuscular vaccination results in mice showed that it caused the strongest neutralizing antibody response (protection against viral entry into cells) against SARS-CoV-2.  Additional tests in mice and hamsters showed that PTX-COVID19-B induced strong antibody-based and T cell-based immune responses and protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from both productive SARS-CoV-2 infection and moderate/severe lung inflammation.  After vaccination with PTX-COVID19-B, serum collected from mice was able to neutralize SARS-CoV-2 VOCs Alpha, Beta, Gamma, and Delta.  Mild, transient effects on body weight observed in some vaccinated mice were resolved within one week.  Overall, vaccination was well tolerated by both mice and hamsters.  Based on these results, PTX-COVID19-B was authorized by Health Canada to enter Phase 1 and Phase 2 clinical trials and results of these trials have now been published.

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Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B. Jun Liu, Patrick Budylowski, Reuben Samson, Bryan D. Griffin, Giorgi Babuadze, Bhavisha Rathod, Karen Colwill, Jumai A. Abioye, Jordan A. Schwartz, Ryan Law, Lily Yip, Sang Kyun Ahn, Serena Chau, Maedeh Naghibosadat, Yuko Arita, Queenie Hu, Feng Yun Yue, Arinjay Banerjee, W. Rod Hardy, Karen Mossman, Samira Mubareka, Robert A. Kozak, Michael S. Pollanen, Natalia Martin Orozco, Anne-Claude Gingras, Eric G. Marcusson, Mario A. Ostrowski. Science Advances. 2022.01.19.9815; https://www.science.org/doi/10.1126/sciadv.abj9815