Cargando…

Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice

Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support the development of vaccine candidates to rapidly improve the available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing vaccine platform to target SARS-CoV-2...

Descripción completa

Detalles Bibliográficos
Autores principales: Fisher, Eva, Padula, Laura, Podack, Kristin, O’Neill, Katelyn, Seavey, Matthew M., Jayaraman, Padmini, Jasuja, Rahul, Strbo, Natasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873992/
https://www.ncbi.nlm.nih.gov/pubmed/33584668
http://dx.doi.org/10.3389/fimmu.2020.602254
_version_ 1783649493999157248
author Fisher, Eva
Padula, Laura
Podack, Kristin
O’Neill, Katelyn
Seavey, Matthew M.
Jayaraman, Padmini
Jasuja, Rahul
Strbo, Natasa
author_facet Fisher, Eva
Padula, Laura
Podack, Kristin
O’Neill, Katelyn
Seavey, Matthew M.
Jayaraman, Padmini
Jasuja, Rahul
Strbo, Natasa
author_sort Fisher, Eva
collection PubMed
description Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support the development of vaccine candidates to rapidly improve the available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing vaccine platform to target SARS-CoV-2. Here, we generated cellular heat shock chaperone protein, glycoprotein 96 (gp96), to deliver SARS-CoV-2 protein S (spike) to the immune system and to induce cell-mediated immune responses. We showed that our vaccine platform effectively stimulates a robust cellular immune response against protein S. Moreover, we confirmed that gp96-Ig, secreted from allogeneic cells expressing full-length protein S, generates powerful, protein S polyepitope-specific CD4+ and CD8+ T cell responses in both lung interstitium and airways. These findings were further strengthened by the observation that protein-S -specific CD8+ T cells were induced in human leukocyte antigen HLA-A2.1 transgenic mice thus providing encouraging translational data that the vaccine is likely to work in humans, in the context of SARS-CoV-2 antigen presentation.
format Online
Article
Text
id pubmed-7873992
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78739922021-02-11 Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice Fisher, Eva Padula, Laura Podack, Kristin O’Neill, Katelyn Seavey, Matthew M. Jayaraman, Padmini Jasuja, Rahul Strbo, Natasa Front Immunol Immunology Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support the development of vaccine candidates to rapidly improve the available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing vaccine platform to target SARS-CoV-2. Here, we generated cellular heat shock chaperone protein, glycoprotein 96 (gp96), to deliver SARS-CoV-2 protein S (spike) to the immune system and to induce cell-mediated immune responses. We showed that our vaccine platform effectively stimulates a robust cellular immune response against protein S. Moreover, we confirmed that gp96-Ig, secreted from allogeneic cells expressing full-length protein S, generates powerful, protein S polyepitope-specific CD4+ and CD8+ T cell responses in both lung interstitium and airways. These findings were further strengthened by the observation that protein-S -specific CD8+ T cells were induced in human leukocyte antigen HLA-A2.1 transgenic mice thus providing encouraging translational data that the vaccine is likely to work in humans, in the context of SARS-CoV-2 antigen presentation. Frontiers Media S.A. 2021-01-26 /pmc/articles/PMC7873992/ /pubmed/33584668 http://dx.doi.org/10.3389/fimmu.2020.602254 Text en Copyright © 2021 Fisher, Padula, Podack, O’Neill, Seavey, Jayaraman, Jasuja and Strbo http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fisher, Eva
Padula, Laura
Podack, Kristin
O’Neill, Katelyn
Seavey, Matthew M.
Jayaraman, Padmini
Jasuja, Rahul
Strbo, Natasa
Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
title Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
title_full Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
title_fullStr Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
title_full_unstemmed Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
title_short Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
title_sort induction of sars-cov-2 protein s-specific cd8+ t cells in the lungs of gp96-ig-s vaccinated mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873992/
https://www.ncbi.nlm.nih.gov/pubmed/33584668
http://dx.doi.org/10.3389/fimmu.2020.602254
work_keys_str_mv AT fishereva inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT padulalaura inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT podackkristin inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT oneillkatelyn inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT seaveymatthewm inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT jayaramanpadmini inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT jasujarahul inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice
AT strbonatasa inductionofsarscov2proteinsspecificcd8tcellsinthelungsofgp96igsvaccinatedmice