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

Author:

Liu Jun1ORCID,Budylowski Patrick12,Samson Reuben34,Griffin Bryan D.5,Babuadze Giorgi5,Rathod Bhavisha4ORCID,Colwill Karen4ORCID,Abioye Jumai A.6,Schwartz Jordan A.6ORCID,Law Ryan7,Yip Lily5ORCID,Ahn Sang Kyun3,Chau Serena7,Naghibosadat Maedeh5,Arita Yuko6ORCID,Hu Queenie4,Yue Feng Yun1ORCID,Banerjee Arinjay8910ORCID,Hardy W. Rod4ORCID,Mossman Karen11ORCID,Mubareka Samira512ORCID,Kozak Robert A.5,Pollanen Michael S.12ORCID,Martin Orozco Natalia6,Gingras Anne-Claude34ORCID,Marcusson Eric G.613ORCID,Ostrowski Mario A.1714ORCID

Affiliation:

1. Department of Medicine, University of Toronto, Toronto, ON, Canada.

2. Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

3. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

4. Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.

5. Sunnybrook Research Institute, Toronto, ON, Canada.

6. Providence Therapeutics Holdings Inc., Calgary, AB, Canada.

7. Department of Immunology, University of Toronto, Toronto, ON, Canada.

8. Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.

9. Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada.

10. Department of Biology, University of Waterloo, Waterloo, ON, Canada.

11. Department of Medicine, McMaster University, Hamilton, ON, Canada.

12. Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada.

13. Marcusson Consulting, San Francisco, CA, USA.

14. Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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