Cutting edge: Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses

Vineet Joag; Sathi Wijeyesinghe; J. Michael Stolley; Clare F Quarnstrom; Thamotharampillai Dileepan; Andrew G. Soerens; Jules A. Sangala; Stephen D O'flanagan; Noah V. Gavil; Sung Wook Hong; Siddheshvar Bhela; Sailaja Gangadhara; Eyob Weyu; William E. Matchett; Joshua Thiede; Venkatramana Krishna; Maxim C.J. Cheeran; Tyler D. Bold; Rama Amara; Peter Southern; Geoffrey T. Hart; Luca Schifanella; Vaiva Vezys; Marc K. Jenkins; Ryan A. Langlois; David Masopust

doi:10.4049/jimmunol.2001400

Cutting edge: Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses

Vineet Joag, Sathi Wijeyesinghe, J. Michael Stolley, Clare F Quarnstrom, Thamotharampillai Dileepan, Andrew G. Soerens, Jules A. Sangala, Stephen D O'flanagan, Noah V. Gavil, Sung Wook Hong, Siddheshvar Bhela, Sailaja Gangadhara, Eyob Weyu, William E. Matchett, Joshua Thiede, Venkatramana Krishna, Maxim C.J. Cheeran, Tyler D. Bold, Rama Amara, Peter SouthernGeoffrey T. Hart, Luca Schifanella, Vaiva Vezys, Marc K. Jenkins, Ryan A. Langlois, David Masopust

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Pages (from-to)	931-935
Number of pages	5
Journal	Journal of Immunology
Volume	206
Issue number	5
DOIs	https://doi.org/10.4049/jimmunol.2001400
State	Published - Jan 13 2021

Bibliographical note

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.

Keywords

Angiotensin-Converting Enzyme 2/genetics
Animals
CD8-Positive T-Lymphocytes/immunology
COVID-19/immunology
COVID-19 Vaccines/immunology
Cells, Cultured
Coronavirus Nucleocapsid Proteins/immunology
Disease Models, Animal
Epitopes, T-Lymphocyte/immunology
Female
Genetic Vectors/immunology
HLA-A2 Antigen/immunology
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
SARS-CoV-2/immunology
Vaccination/methods

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4049/jimmunol.2001400

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Joag, V., Wijeyesinghe, S., Stolley, J. M., Quarnstrom, C. F., Dileepan, T., Soerens, A. G., Sangala, J. A., O'flanagan, S. D., Gavil, N. V., Hong, S. W., Bhela, S., Gangadhara, S., Weyu, E., Matchett, W. E., Thiede, J., Krishna, V., Cheeran, M. C. J., Bold, T. D., Amara, R., ... Masopust, D. (2021). Cutting edge: Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses. Journal of Immunology, 206(5), 931-935. https://doi.org/10.4049/jimmunol.2001400

Joag, V, Wijeyesinghe, S, Stolley, JM, Quarnstrom, CF , Dileepan, T , Soerens, AG, Sangala, JA, O'flanagan, SD, Gavil, NV, Hong, SW, Bhela, S, Gangadhara, S, Weyu, E, Matchett, WE, Thiede, J, Krishna, V , Cheeran, MCJ , Bold, TD, Amara, R, Southern, P , Hart, GT , Schifanella, L , Vezys, V , Jenkins, MK , Langlois, RA & Masopust, D 2021, 'Cutting edge: Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses', Journal of Immunology, vol. 206, no. 5, pp. 931-935. https://doi.org/10.4049/jimmunol.2001400

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title = "Cutting edge: Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses",

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.",

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author = "Vineet Joag and Sathi Wijeyesinghe and Stolley, {J. Michael} and Quarnstrom, {Clare F} and Thamotharampillai Dileepan and Soerens, {Andrew G.} and Sangala, {Jules A.} and O'flanagan, {Stephen D} and Gavil, {Noah V.} and Hong, {Sung Wook} and Siddheshvar Bhela and Sailaja Gangadhara and Eyob Weyu and Matchett, {William E.} and Joshua Thiede and Venkatramana Krishna and Cheeran, {Maxim C.J.} and Bold, {Tyler D.} and Rama Amara and Peter Southern and Hart, {Geoffrey T.} and Luca Schifanella and Vaiva Vezys and Jenkins, {Marc K.} and Langlois, {Ryan A.} and David Masopust",

note = "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: {\textcopyright} 2021 American Association of Immunologists. All rights reserved.",

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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.

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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.

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KW - Mice, Transgenic

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Cutting edge: Mouse sars-cov-2 epitope reveals infection and vaccine-elicited cd8 t cell responses

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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