CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology
We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/11/1346 |
| _version_ | 1797508271903342592 |
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| author | Jennifer K. DeMarco Joshua M. Royal William E. Severson Jon D. Gabbard Steve Hume Josh Morton Kelsi Swope Carrie A. Simpson John W. Shepherd Barry Bratcher Kenneth E. Palmer Gregory P. Pogue |
| author_facet | Jennifer K. DeMarco Joshua M. Royal William E. Severson Jon D. Gabbard Steve Hume Josh Morton Kelsi Swope Carrie A. Simpson John W. Shepherd Barry Bratcher Kenneth E. Palmer Gregory P. Pogue |
| author_sort | Jennifer K. DeMarco |
| collection | DOAJ |
| description | We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19. |
| first_indexed | 2024-03-10T05:00:36Z |
| format | Article |
| id | doaj.art-d948abd924354895b2c5b1c46d082bd9 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T05:00:36Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d948abd924354895b2c5b1c46d082bd92023-11-23T01:53:30ZengMDPI AGVaccines2076-393X2021-11-01911134610.3390/vaccines9111346CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated ImmunopathologyJennifer K. DeMarco0Joshua M. Royal1William E. Severson2Jon D. Gabbard3Steve Hume4Josh Morton5Kelsi Swope6Carrie A. Simpson7John W. Shepherd8Barry Bratcher9Kenneth E. Palmer10Gregory P. Pogue11Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USACenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USACenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USACenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville, Louisville, KY 40202, USAKentucky BioProcessing, Inc., Owensboro, KY 42301, USAWe developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.https://www.mdpi.com/2076-393X/9/11/1346SARS-CoV-2COVID-19betacoronavirusvaccinebetacoronaviridaeTMV |
| spellingShingle | Jennifer K. DeMarco Joshua M. Royal William E. Severson Jon D. Gabbard Steve Hume Josh Morton Kelsi Swope Carrie A. Simpson John W. Shepherd Barry Bratcher Kenneth E. Palmer Gregory P. Pogue CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology Vaccines SARS-CoV-2 COVID-19 betacoronavirus vaccine betacoronaviridae TMV |
| title | CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology |
| title_full | CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology |
| title_fullStr | CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology |
| title_full_unstemmed | CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology |
| title_short | CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology |
| title_sort | cov rbd121 np vaccine candidate protects against symptomatic disease following sars cov 2 challenge in k18 hace2 mice and induces protective responses that prevent covid 19 associated immunopathology |
| topic | SARS-CoV-2 COVID-19 betacoronavirus vaccine betacoronaviridae TMV |
| url | https://www.mdpi.com/2076-393X/9/11/1346 |
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