| Literature DB >> 33441437 |
Vineet Joag1,2, Sathi Wijeyesinghe1,2, J Michael Stolley1,2, Clare F Quarnstrom1,2, Thamotharampillai Dileepan1,2, Andrew G Soerens1,2, Jules A Sangala2,3, Stephen D O'Flanagan1,2, Noah V Gavil1,2, Sung-Wook Hong1,2, Siddheshvar Bhela1,2, Sailaja Gangadhara4, Eyob Weyu1,2, William E Matchett1,2, Joshua Thiede2,3, Venkatramana Krishna5, Maxim C-J Cheeran5, Tyler D Bold2,3, Rama Amara4, Peter Southern1, Geoffrey T Hart2,3, Luca Schifanella6, Vaiva Vezys1,2, Marc K Jenkins7,2, Ryan A Langlois7,2, David Masopust7,2.
Abstract
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.Entities:
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Year: 2021 PMID： 33441437 PMCID： PMC8136468 DOI： 10.4049/jimmunol.2001400
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422