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.
Bibliographical noteFunding Information:
This work was supported by the Office of the Dean of the University of Minnesota Medical School, the Howard Hughes Medical Institute Faculty Scholar program (to D.M.), the Canadian Institutes of Health Research Fellowship (to V.J.), and National Institutes of Health Award F30 DK114942 (to S.W.).
© 2021 American Association of Immunologists. All rights reserved.
- Angiotensin-Converting Enzyme 2/genetics
- CD8-Positive T-Lymphocytes/immunology
- COVID-19 Vaccines/immunology
- Cells, Cultured
- Coronavirus Nucleocapsid Proteins/immunology
- Disease Models, Animal
- Epitopes, T-Lymphocyte/immunology
- Genetic Vectors/immunology
- HLA-A2 Antigen/immunology
- Mice, Inbred C57BL
- Mice, Transgenic
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural