Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity
© 2021 The Authors. Published under the terms of the CC BY 4.0 license..
Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
EMBO reports - 22(2021), 8 vom: 04. Aug., Seite e52447 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chauveau, Lise [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.08.2021 Date Revised 13.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/embr.202152447 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326899588 |
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| 100 | 1 | |a Chauveau, Lise |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 09.08.2021 | ||
| 500 | |a Date Revised 13.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a cGAMP | |
| 650 | 4 | |a influenza A virus | |
| 650 | 4 | |a type I interferon | |
| 650 | 4 | |a viral vaccine vector | |
| 650 | 7 | |a Influenza Vaccines |2 NLM | |
| 650 | 7 | |a Nucleotides, Cyclic |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a Vaccines, Virus-Like Particle |2 NLM | |
| 650 | 7 | |a cyclic guanosine monophosphate-adenosine monophosphate |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 700 | 1 | |a Bridgeman, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Tiong K |e verfasserin |4 aut | |
| 700 | 1 | |a Beveridge, Ryan |e verfasserin |4 aut | |
| 700 | 1 | |a Frost, Joe N |e verfasserin |4 aut | |
| 700 | 1 | |a Rijal, Pramila |e verfasserin |4 aut | |
| 700 | 1 | |a Pedroza-Pacheco, Isabela |e verfasserin |4 aut | |
| 700 | 1 | |a Partridge, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbert-Jaramillo, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Knight, Michael L |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Russell, Rebecca A |e verfasserin |4 aut | |
| 700 | 1 | |a Borrow, Persephone |e verfasserin |4 aut | |
| 700 | 1 | |a Drakesmith, Hal |e verfasserin |4 aut | |
| 700 | 1 | |a Townsend, Alain R |e verfasserin |4 aut | |
| 700 | 1 | |a Rehwinkel, Jan |e verfasserin |4 aut | |
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