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

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.

• Authors: 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
• Journal: Science advances (Sci Adv) Vol. 8 Issue 3 Pg. eabj9815 (Jan 21 2022) ISSN: 2375-2548 [Electronic] United States
• PMID: 35044832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• Lipid Nanoparticles
• Liposomes
• Spike Glycoprotein, Coronavirus
• Vaccines, Synthetic
• mRNA Vaccine
• mRNA Vaccines
• spike protein, SARS-CoV-2

Topics

• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• CD4 Lymphocyte Count
• CD8-Positive T-Lymphocytes (immunology)
• COVID-19 (immunology, prevention & control)
• COVID-19 Vaccines (adverse effects, immunology)
• 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
• SARS-CoV-2 (immunology)
• Spike Glycoprotein, Coronavirus (genetics, immunology)
• Th1 Cells (immunology)
• Vaccines, Synthetic (immunology)
• mRNA Vaccines (immunology)