Cutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses
| Autor: | J. Michael Stolley, Peter J. Southern, Siddheshvar Bhela, Thamotharampillai Dileepan, Maxim C.-J. Cheeran, Vineet Joag, Marc K. Jenkins, Sathi Wijeyesinghe, Joshua M. Thiede, Luca Schifanella, Jules A. Sangala, Clare F. Quarnstrom, Geoffrey T. Hart, Stephen D O'Flanagan, Sung-Wook Hong, Venkatramana D. Krishna, William E. Matchett, Noah V. Gavil, David Masopust, Sailaja Gangadhara, Tyler D. Bold, Eyob Weyu, Ryan A. Langlois, Vaiva Vezys, Rama Rao Amara, Andrew G. Soerens |
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| Rok vydání: | 2020 |
| Předmět: |
COVID-19 Vaccines
T cell viruses Immunology Genetic Vectors Heterologous Epitopes T-Lymphocyte Mice Transgenic Biology CD8-Positive T-Lymphocytes Epitope Article 03 medical and health sciences Mice 0302 clinical medicine Immunity HLA-A2 Antigen medicine Immunology and Allergy Cytotoxic T cell Animals Coronavirus Nucleocapsid Proteins Humans Cells Cultured SARS-CoV-2 Vaccination COVID-19 Virology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Immunization Humoral immunity Female Angiotensin-Converting Enzyme 2 030215 immunology |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 |
| Popis: | The magnitude of SARS-CoV-2–specific T cell responses correlates inversely with human disease severity, suggesting T cell involvement in primary control. Whereas many COVID-19 vaccines focus on establishing humoral immunity to viral spike protein, vaccine-elicited T cell immunity may bolster durable protection or cross-reactivity with viral variants. To better enable mechanistic and vaccination studies in mice, we identified a dominant CD8 T cell SARS-CoV-2 nucleoprotein epitope. Infection of human ACE2 transgenic mice with SARS-CoV-2 elicited robust responses to H2-Db/N219-227, and 40% of HLA-A*02+ COVID-19 PBMC samples isolated from hospitalized patients responded to this peptide in culture. In mice, i.m. prime-boost nucleoprotein vaccination with heterologous vectors favored systemic CD8 T cell responses, whereas intranasal boosting favored respiratory immunity. In contrast, a single i.v. immunization with recombinant adenovirus established robust CD8 T cell memory both systemically and in the respiratory mucosa. |
| Databáze: | OpenAIRE |
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