1. Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.
- Author
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Liu J, Budylowski P, Samson R, Griffin BD, Babuadze G, Rathod B, Colwill K, Abioye JA, Schwartz JA, Law R, Yip L, Ahn SK, Chau S, Naghibosadat M, Arita Y, Hu Q, Yue FY, Banerjee A, Hardy WR, Mossman K, Mubareka S, Kozak RA, Pollanen MS, Martin Orozco N, Gingras AC, Marcusson EG, and Ostrowski MA
- Subjects
- Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes immunology, COVID-19 immunology, COVID-19 Vaccines adverse effects, Canada, Cell Line, Cricetinae, Drug Evaluation, Preclinical, Female, HEK293 Cells, Humans, Immunity, Cellular immunology, Immunity, Humoral immunology, Liposomes pharmacology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Nanoparticles, Spike Glycoprotein, Coronavirus genetics, Th1 Cells immunology, COVID-19 prevention & control, COVID-19 Vaccines immunology, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology, Vaccines, Synthetic immunology, mRNA Vaccines immunology
- Abstract
Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle–formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely 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 SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.
- Published
- 2022
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