Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

• Published in: Science advances Vol. 8; no. 3; p. eabj9815
• Main Authors: Liu, Jun, Budylowski, Patrick, Samson, Reuben, Griffin, Bryan D, Babuadze, Giorgi, Rathod, Bhavisha, Colwill, Karen, Abioye, Jumai A, Schwartz, Jordan A, Law, Ryan, Yip, Lily, Ahn, Sang Kyun, Chau, Serena, Naghibosadat, Maedeh, Arita, Yuko, Hu, Queenie, Yue, Feng Yun, Banerjee, Arinjay, Hardy, W Rod, Mossman, Karen, Mubareka, Samira, Kozak, Robert A, Pollanen, Michael S, Martin Orozco, Natalia, Gingras, Anne-Claude, Marcusson, Eric G, Ostrowski, Mario A
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 21.01.2022
• Subjects: Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Biomedicine and Life Sciences; Canada; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes - immunology; Cell Line; Coronavirus; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - adverse effects; COVID-19 Vaccines - immunology; Cricetinae; Drug Evaluation, Preclinical; Female; HEK293 Cells; Humans; Immunity, Cellular - immunology; Immunity, Humoral - immunology; Immunology; Liposomes - pharmacology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; mRNA Vaccines - immunology; Nanoparticles; SARS-CoV-2 - immunology; SciAdv r-articles; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Th1 Cells - immunology; Vaccines, Synthetic - immunology; Canada
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abj9815

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.