Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection
| Autor: | Mathieu J.F. Crupi, Douglas J. Mahoney, Rebecca C. Auer, Sarah Tucker, Adrian Pelin, D. William Cameron, Taylor R Jamieson, Ricardo Marius, John C. Bell, Réjean Lapointe, Kyle Potts, Nikolas T. Martin, Zaid Taha, Ragunath Singaravelu, Taha Azad, Jean-François Cailhier, Joanna Poutou, Bradley Austin, Jean-Simon Diallo, Emily E.F. Brown, Jack Whelan, Christiano Tanese de Souza, Sarwat T. Khan, Reza Rezaei, Julia Petryk, Carolina S. Ilkow, Stephen Boulton, Jonathan B. Angel, Jaahnavi Dave, Xiaohong He, Abera Surendran |
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| Rok vydání: | 2022 |
| Předmět: |
COVID-19 Vaccines
T-Lymphocytes Antibodies Viral immune response Virus RBD Mice chemistry.chemical_compound Immune system Antigen vaccine Drug Discovery Pandemic Genetics Animals Medicine Vector (molecular biology) Molecular Biology Pharmacology Vaccines biology SARS-CoV-2 business.industry Immunogenicity Immunity COVID-19 Antibodies Neutralizing Virology vaccinia virus single dose chemistry Spike Glycoprotein Coronavirus biology.protein Molecular Medicine Original Article Vaccinia Antibody business |
| Zdroj: | Molecular Therapy |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2021.10.008 |
| Popis: | The coronavirus disease 2019 (COVID-19) pandemic requires the continued development of safe, long-lasting, and efficacious vaccines for preventive responses to major outbreaks around the world, and especially in isolated and developing countries. To combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we characterize a temperature-stable vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain (RBD) antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in animal models. Our vaccine induces high levels of SARS-CoV-2 neutralizing antibodies and favorable T cell responses, while maintaining an optimal safety profile in mice and cynomolgus macaques. We demonstrate robust immune responses and protective immunity against SARS-CoV-2 variants after only a single dose. Together, these findings support further development of our novel and versatile vaccine platform as an alternative or complementary approach to current vaccines. Graphical abstract To combat SARS-CoV-2, we characterize a novel vaccine candidate (TOH-Vac1) that uses a replication-competent, attenuated vaccinia virus as a vector to express a membrane-tethered spike receptor binding domain antigen. We evaluate the effects of dose escalation and administration routes on vaccine safety, efficacy, and immunogenicity in mice and cynomolgus macaques. |
| Databáze: | OpenAIRE |
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