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Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice

Current vaccines against SARS-CoV-2 substantially reduce mortality, but protection against infection is less effective. Enhancing immunity in the respiratory tract, via mucosal vaccination, may provide protection against infection and minimise viral spread. Here, we report testing of a subunit vacci...

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Autores principales: Ashhurst, Anneliese S., Johansen, Matt D., Maxwell, Joshua W. C., Stockdale, Skye, Ashley, Caroline L., Aggarwal, Anupriya, Siddiquee, Rezwan, Miemczyk, Stefan, Nguyen, Duc H., Mackay, Joel P., Counoupas, Claudio, Byrne, Scott N., Turville, Stuart, Steain, Megan, Triccas, James A., Hansbro, Philip M., Payne, Richard J., Britton, Warwick J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665025/
https://www.ncbi.nlm.nih.gov/pubmed/36379950
http://dx.doi.org/10.1038/s41467-022-34297-3
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author Ashhurst, Anneliese S.
Johansen, Matt D.
Maxwell, Joshua W. C.
Stockdale, Skye
Ashley, Caroline L.
Aggarwal, Anupriya
Siddiquee, Rezwan
Miemczyk, Stefan
Nguyen, Duc H.
Mackay, Joel P.
Counoupas, Claudio
Byrne, Scott N.
Turville, Stuart
Steain, Megan
Triccas, James A.
Hansbro, Philip M.
Payne, Richard J.
Britton, Warwick J.
author_facet Ashhurst, Anneliese S.
Johansen, Matt D.
Maxwell, Joshua W. C.
Stockdale, Skye
Ashley, Caroline L.
Aggarwal, Anupriya
Siddiquee, Rezwan
Miemczyk, Stefan
Nguyen, Duc H.
Mackay, Joel P.
Counoupas, Claudio
Byrne, Scott N.
Turville, Stuart
Steain, Megan
Triccas, James A.
Hansbro, Philip M.
Payne, Richard J.
Britton, Warwick J.
author_sort Ashhurst, Anneliese S.
collection PubMed
description Current vaccines against SARS-CoV-2 substantially reduce mortality, but protection against infection is less effective. Enhancing immunity in the respiratory tract, via mucosal vaccination, may provide protection against infection and minimise viral spread. Here, we report testing of a subunit vaccine in mice, consisting of SARS-CoV-2 Spike protein with a TLR2-stimulating adjuvant (Pam(2)Cys), delivered to mice parenterally or mucosally. Both routes of vaccination induce substantial neutralising antibody (nAb) titres, however, mucosal vaccination uniquely generates anti-Spike IgA, increases nAb in the serum and airways, and increases lung CD4(+) T-cell responses. TLR2 is expressed by respiratory epithelia and immune cells. Using TLR2 deficient chimeric mice, we determine that TLR2 expression in either compartment facilitates early innate responses to mucosal vaccination. By contrast, TLR2 on hematopoietic cells is essential for optimal lung-localised, antigen-specific responses. In K18-hACE2 mice, vaccination provides complete protection against disease and sterilising lung immunity against SARS-CoV-2, with a short-term non-specific protective effect from mucosal Pam(2)Cys alone. These data support mucosal vaccination as a strategy to improve protection in the respiratory tract against SARS-CoV-2 and other respiratory viruses.
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spelling pubmed-96650252022-11-16 Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice Ashhurst, Anneliese S. Johansen, Matt D. Maxwell, Joshua W. C. Stockdale, Skye Ashley, Caroline L. Aggarwal, Anupriya Siddiquee, Rezwan Miemczyk, Stefan Nguyen, Duc H. Mackay, Joel P. Counoupas, Claudio Byrne, Scott N. Turville, Stuart Steain, Megan Triccas, James A. Hansbro, Philip M. Payne, Richard J. Britton, Warwick J. Nat Commun Article Current vaccines against SARS-CoV-2 substantially reduce mortality, but protection against infection is less effective. Enhancing immunity in the respiratory tract, via mucosal vaccination, may provide protection against infection and minimise viral spread. Here, we report testing of a subunit vaccine in mice, consisting of SARS-CoV-2 Spike protein with a TLR2-stimulating adjuvant (Pam(2)Cys), delivered to mice parenterally or mucosally. Both routes of vaccination induce substantial neutralising antibody (nAb) titres, however, mucosal vaccination uniquely generates anti-Spike IgA, increases nAb in the serum and airways, and increases lung CD4(+) T-cell responses. TLR2 is expressed by respiratory epithelia and immune cells. Using TLR2 deficient chimeric mice, we determine that TLR2 expression in either compartment facilitates early innate responses to mucosal vaccination. By contrast, TLR2 on hematopoietic cells is essential for optimal lung-localised, antigen-specific responses. In K18-hACE2 mice, vaccination provides complete protection against disease and sterilising lung immunity against SARS-CoV-2, with a short-term non-specific protective effect from mucosal Pam(2)Cys alone. These data support mucosal vaccination as a strategy to improve protection in the respiratory tract against SARS-CoV-2 and other respiratory viruses. Nature Publishing Group UK 2022-11-15 /pmc/articles/PMC9665025/ /pubmed/36379950 http://dx.doi.org/10.1038/s41467-022-34297-3 Text en © The Author(s) 2022 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
Ashhurst, Anneliese S.
Johansen, Matt D.
Maxwell, Joshua W. C.
Stockdale, Skye
Ashley, Caroline L.
Aggarwal, Anupriya
Siddiquee, Rezwan
Miemczyk, Stefan
Nguyen, Duc H.
Mackay, Joel P.
Counoupas, Claudio
Byrne, Scott N.
Turville, Stuart
Steain, Megan
Triccas, James A.
Hansbro, Philip M.
Payne, Richard J.
Britton, Warwick J.
Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
title Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
title_full Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
title_fullStr Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
title_full_unstemmed Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
title_short Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice
title_sort mucosal tlr2-activating protein-based vaccination induces potent pulmonary immunity and protection against sars-cov-2 in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9665025/
https://www.ncbi.nlm.nih.gov/pubmed/36379950
http://dx.doi.org/10.1038/s41467-022-34297-3
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