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

Autor: Liu J; Department of Medicine, University of Toronto, Toronto, ON, Canada., Budylowski P; Department of Medicine, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Samson R; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada., Griffin BD; Sunnybrook Research Institute, Toronto, ON, Canada., Babuadze G; Sunnybrook Research Institute, Toronto, ON, Canada., Rathod B; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada., Colwill K; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada., Abioye JA; Providence Therapeutics Holdings Inc., Calgary, AB, Canada., Schwartz JA; Providence Therapeutics Holdings Inc., Calgary, AB, Canada., Law R; Department of Immunology, University of Toronto, Toronto, ON, Canada., Yip L; Sunnybrook Research Institute, Toronto, ON, Canada., Ahn SK; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Chau S; Department of Immunology, University of Toronto, Toronto, ON, Canada., Naghibosadat M; Sunnybrook Research Institute, Toronto, ON, Canada., Arita Y; Providence Therapeutics Holdings Inc., Calgary, AB, Canada., Hu Q; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada., Yue FY; Department of Medicine, University of Toronto, Toronto, ON, Canada., Banerjee A; Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.; Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada.; Department of Biology, University of Waterloo, Waterloo, ON, Canada., Hardy WR; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada., Mossman K; Department of Medicine, McMaster University, Hamilton, ON, Canada., Mubareka S; Sunnybrook Research Institute, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada., Kozak RA; Sunnybrook Research Institute, Toronto, ON, Canada., Pollanen MS; Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada., Martin Orozco N; Providence Therapeutics Holdings Inc., Calgary, AB, Canada., Gingras AC; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada., Marcusson EG; Providence Therapeutics Holdings Inc., Calgary, AB, Canada.; Marcusson Consulting, San Francisco, CA, USA., Ostrowski MA; Department of Medicine, University of Toronto, Toronto, ON, Canada.; Department of Immunology, University of Toronto, Toronto, ON, Canada.; Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Jan 21; Vol. 8 (3), pp. eabj9815. Date of Electronic Publication: 2022 Jan 19.
DOI: 10.1126/sciadv.abj9815
Abstrakt: 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.
Databáze: MEDLINE