Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice.
Ashhurst, AS
Johansen, MD
Maxwell, JWC
Stockdale, S
Ashley, CL
Aggarwal, A
Siddiquee, R
Miemczyk, S
Nguyen, DH
Mackay, JP
Counoupas, C
Byrne, SN
Turville, S
Steain, M
Triccas, JA
Hansbro, PM
Payne, RJ
Britton, WJ
- Publisher:
- NATURE PORTFOLIO
- Publication Type:
- Journal Article
- Citation:
- Nat Commun, 2022, 13, (1), pp. 6972
- Issue Date:
- 2022-11-15
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Ashhurst, AS | |
dc.contributor.author | Johansen, MD | |
dc.contributor.author | Maxwell, JWC | |
dc.contributor.author | Stockdale, S | |
dc.contributor.author | Ashley, CL | |
dc.contributor.author | Aggarwal, A | |
dc.contributor.author | Siddiquee, R | |
dc.contributor.author | Miemczyk, S | |
dc.contributor.author | Nguyen, DH | |
dc.contributor.author | Mackay, JP | |
dc.contributor.author | Counoupas, C | |
dc.contributor.author | Byrne, SN | |
dc.contributor.author | Turville, S | |
dc.contributor.author | Steain, M | |
dc.contributor.author | Triccas, JA | |
dc.contributor.author | Hansbro, PM | |
dc.contributor.author | Payne, RJ | |
dc.contributor.author | Britton, WJ | |
dc.date.accessioned | 2023-02-14T00:43:12Z | |
dc.date.available | 2022-10-20 | |
dc.date.available | 2023-02-14T00:43:12Z | |
dc.date.issued | 2022-11-15 | |
dc.identifier.citation | Nat Commun, 2022, 13, (1), pp. 6972 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | http://hdl.handle.net/10453/166091 | |
dc.description.abstract | 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 (Pam2Cys), 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 Pam2Cys alone. These data support mucosal vaccination as a strategy to improve protection in the respiratory tract against SARS-CoV-2 and other respiratory viruses. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1175134 | |
dc.relation | http://purl.org/au-research/grants/nhmrc/1153493 | |
dc.relation.ispartof | Nat Commun | |
dc.relation.isbasedon | 10.1038/s41467-022-34297-3 | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Animals | |
dc.subject.mesh | SARS-CoV-2 | |
dc.subject.mesh | Viral Vaccines | |
dc.subject.mesh | Toll-Like Receptor 2 | |
dc.subject.mesh | COVID-19 Vaccines | |
dc.subject.mesh | COVID-19 | |
dc.subject.mesh | Spike Glycoprotein, Coronavirus | |
dc.subject.mesh | Vaccination | |
dc.subject.mesh | Lung | |
dc.subject.mesh | Antibodies, Viral | |
dc.subject.mesh | Immunity, Mucosal | |
dc.subject.mesh | Antibodies, Neutralizing | |
dc.subject.mesh | Lung | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Viral Vaccines | |
dc.subject.mesh | Antibodies, Viral | |
dc.subject.mesh | Vaccination | |
dc.subject.mesh | Immunity, Mucosal | |
dc.subject.mesh | Toll-Like Receptor 2 | |
dc.subject.mesh | Antibodies, Neutralizing | |
dc.subject.mesh | Spike Glycoprotein, Coronavirus | |
dc.subject.mesh | COVID-19 | |
dc.subject.mesh | SARS-CoV-2 | |
dc.subject.mesh | COVID-19 Vaccines | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Animals | |
dc.subject.mesh | SARS-CoV-2 | |
dc.subject.mesh | Viral Vaccines | |
dc.subject.mesh | Toll-Like Receptor 2 | |
dc.subject.mesh | COVID-19 Vaccines | |
dc.subject.mesh | COVID-19 | |
dc.subject.mesh | Spike Glycoprotein, Coronavirus | |
dc.subject.mesh | Vaccination | |
dc.subject.mesh | Lung | |
dc.subject.mesh | Antibodies, Viral | |
dc.subject.mesh | Immunity, Mucosal | |
dc.subject.mesh | Antibodies, Neutralizing | |
dc.title | Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice. | |
dc.type | Journal Article | |
utslib.citation.volume | 13 | |
utslib.location.activity | England | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CFI - Centre for Inflammation | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2023-02-14T00:43:06Z | |
pubs.issue | 1 | |
pubs.publication-status | Published online | |
pubs.volume | 13 | |
utslib.citation.issue | 1 |
Abstract:
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 (Pam2Cys), 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 Pam2Cys 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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