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Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization

Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic pla...

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Autores principales: Lapuente, Dennis, Fuchs, Jana, Willar, Jonas, Vieira Antão, Ana, Eberlein, Valentina, Uhlig, Nadja, Issmail, Leila, Schmidt, Anna, Oltmanns, Friederike, Peter, Antonia Sophia, Mueller-Schmucker, Sandra, Irrgang, Pascal, Fraedrich, Kirsten, Cara, Andrea, Hoffmann, Markus, Pöhlmann, Stefan, Ensser, Armin, Pertl, Cordula, Willert, Torsten, Thirion, Christian, Grunwald, Thomas, Überla, Klaus, Tenbusch, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626513/
https://www.ncbi.nlm.nih.gov/pubmed/34836955
http://dx.doi.org/10.1038/s41467-021-27063-4
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author Lapuente, Dennis
Fuchs, Jana
Willar, Jonas
Vieira Antão, Ana
Eberlein, Valentina
Uhlig, Nadja
Issmail, Leila
Schmidt, Anna
Oltmanns, Friederike
Peter, Antonia Sophia
Mueller-Schmucker, Sandra
Irrgang, Pascal
Fraedrich, Kirsten
Cara, Andrea
Hoffmann, Markus
Pöhlmann, Stefan
Ensser, Armin
Pertl, Cordula
Willert, Torsten
Thirion, Christian
Grunwald, Thomas
Überla, Klaus
Tenbusch, Matthias
author_facet Lapuente, Dennis
Fuchs, Jana
Willar, Jonas
Vieira Antão, Ana
Eberlein, Valentina
Uhlig, Nadja
Issmail, Leila
Schmidt, Anna
Oltmanns, Friederike
Peter, Antonia Sophia
Mueller-Schmucker, Sandra
Irrgang, Pascal
Fraedrich, Kirsten
Cara, Andrea
Hoffmann, Markus
Pöhlmann, Stefan
Ensser, Armin
Pertl, Cordula
Willert, Torsten
Thirion, Christian
Grunwald, Thomas
Überla, Klaus
Tenbusch, Matthias
author_sort Lapuente, Dennis
collection PubMed
description Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (T(RM)); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung T(RM) after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.
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spelling pubmed-86265132021-12-10 Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization Lapuente, Dennis Fuchs, Jana Willar, Jonas Vieira Antão, Ana Eberlein, Valentina Uhlig, Nadja Issmail, Leila Schmidt, Anna Oltmanns, Friederike Peter, Antonia Sophia Mueller-Schmucker, Sandra Irrgang, Pascal Fraedrich, Kirsten Cara, Andrea Hoffmann, Markus Pöhlmann, Stefan Ensser, Armin Pertl, Cordula Willert, Torsten Thirion, Christian Grunwald, Thomas Überla, Klaus Tenbusch, Matthias Nat Commun Article Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (T(RM)); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung T(RM) after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses. Nature Publishing Group UK 2021-11-26 /pmc/articles/PMC8626513/ /pubmed/34836955 http://dx.doi.org/10.1038/s41467-021-27063-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lapuente, Dennis
Fuchs, Jana
Willar, Jonas
Vieira Antão, Ana
Eberlein, Valentina
Uhlig, Nadja
Issmail, Leila
Schmidt, Anna
Oltmanns, Friederike
Peter, Antonia Sophia
Mueller-Schmucker, Sandra
Irrgang, Pascal
Fraedrich, Kirsten
Cara, Andrea
Hoffmann, Markus
Pöhlmann, Stefan
Ensser, Armin
Pertl, Cordula
Willert, Torsten
Thirion, Christian
Grunwald, Thomas
Überla, Klaus
Tenbusch, Matthias
Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
title Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
title_full Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
title_fullStr Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
title_full_unstemmed Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
title_short Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
title_sort protective mucosal immunity against sars-cov-2 after heterologous systemic prime-mucosal boost immunization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626513/
https://www.ncbi.nlm.nih.gov/pubmed/34836955
http://dx.doi.org/10.1038/s41467-021-27063-4
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