TY - JOUR
T1 - Cutting edge
T2 - Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses
AU - Joag, Vineet
AU - Wijeyesinghe, Sathi
AU - Stolley, J. Michael
AU - Quarnstrom, Clare F.
AU - Dileepan, Thamotharampillai
AU - Soerens, Andrew G.
AU - Sangala, Jules A.
AU - O'Flanagan, Stephen D.
AU - Gavil, Noah V.
AU - Hong, Sung Wook
AU - Bhela, Siddheshvar
AU - Gangadhara, Sailaja
AU - Weyu, Eyob
AU - Matchett, William E.
AU - Thiede, Joshua
AU - Krishna, Venkatramana
AU - Cheeran, Maxim C.J.
AU - Bold, Tyler D.
AU - Amara, Rama
AU - Southern, Peter
AU - Hart, Geoffrey T.
AU - Schifanella, Luca
AU - Vezys, Vaiva
AU - Jenkins, Marc K.
AU - Langlois, Ryan A.
AU - Masopust, David
N1 - Funding 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.).
Publisher Copyright:
© 2021 American Association of Immunologists. All rights reserved.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.2001400
DO - 10.4049/jimmunol.2001400
M3 - Article
C2 - 33441437
AN - SCOPUS:85101230859
SN - 0022-1767
VL - 206
SP - 931
EP - 935
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -
