Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters
Abstract With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13819-5 |
| _version_ | 1811241196196986880 |
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| author | Felicity C. Stark Bassel Akache Lise Deschatelets Anh Tran Matthew Stuible Yves Durocher Michael J. McCluskie Gerard Agbayani Renu Dudani Blair A. Harrison Tyler M. Renner Shawn R. Makinen Jegarubee Bavananthasivam Diana Duque Martin Gagne Joseph Zimmermann C. David Zarley Terrence R. Cochrane Martin Handfield |
| author_facet | Felicity C. Stark Bassel Akache Lise Deschatelets Anh Tran Matthew Stuible Yves Durocher Michael J. McCluskie Gerard Agbayani Renu Dudani Blair A. Harrison Tyler M. Renner Shawn R. Makinen Jegarubee Bavananthasivam Diana Duque Martin Gagne Joseph Zimmermann C. David Zarley Terrence R. Cochrane Martin Handfield |
| author_sort | Felicity C. Stark |
| collection | DOAJ |
| description | Abstract With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine. |
| first_indexed | 2024-04-12T13:32:06Z |
| format | Article |
| id | doaj.art-75d13e574ac142e0965e0c8633e1ee5d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T13:32:06Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-75d13e574ac142e0965e0c8633e1ee5d2022-12-22T03:31:08ZengNature PortfolioScientific Reports2045-23222022-06-0112111110.1038/s41598-022-13819-5Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamstersFelicity C. Stark0Bassel Akache1Lise Deschatelets2Anh Tran3Matthew Stuible4Yves Durocher5Michael J. McCluskie6Gerard Agbayani7Renu Dudani8Blair A. Harrison9Tyler M. Renner10Shawn R. Makinen11Jegarubee Bavananthasivam12Diana Duque13Martin Gagne14Joseph Zimmermann15C. David Zarley16Terrence R. Cochrane17Martin Handfield18National Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsNational Research Council Canada, Human Health TherapeuticsBiodextris Inc.Inspirevax Inc.Oragenics, Inc.Oragenics, Inc.Oragenics, Inc.Abstract With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.https://doi.org/10.1038/s41598-022-13819-5 |
| spellingShingle | Felicity C. Stark Bassel Akache Lise Deschatelets Anh Tran Matthew Stuible Yves Durocher Michael J. McCluskie Gerard Agbayani Renu Dudani Blair A. Harrison Tyler M. Renner Shawn R. Makinen Jegarubee Bavananthasivam Diana Duque Martin Gagne Joseph Zimmermann C. David Zarley Terrence R. Cochrane Martin Handfield Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters Scientific Reports |
| title | Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters |
| title_full | Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters |
| title_fullStr | Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters |
| title_full_unstemmed | Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters |
| title_short | Intranasal immunization with a proteosome-adjuvanted SARS-CoV-2 spike protein-based vaccine is immunogenic and efficacious in mice and hamsters |
| title_sort | intranasal immunization with a proteosome adjuvanted sars cov 2 spike protein based vaccine is immunogenic and efficacious in mice and hamsters |
| url | https://doi.org/10.1038/s41598-022-13819-5 |
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