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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 COVID-19 betacoronavirus vaccine betacoronaviridae TMV Medicine R
Acceso en línea:	https://doaj.org/article/d948abd924354895b2c5b1c46d082bd9
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spelling	oai:doaj.org-article:d948abd924354895b2c5b1c46d082bd92021-11-25T19:11:30ZCoV-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 Immunopathology10.3390/vaccines91113462076-393Xhttps://doaj.org/article/d948abd924354895b2c5b1c46d082bd92021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1346https://doaj.org/toc/2076-393XWe 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.Jennifer K. DeMarcoJoshua M. RoyalWilliam E. SeversonJon D. GabbardSteve HumeJosh MortonKelsi SwopeCarrie A. SimpsonJohn W. ShepherdBarry BratcherKenneth E. PalmerGregory P. PogueMDPI AGarticleSARS-CoV-2COVID-19betacoronavirusvaccinebetacoronaviridaeTMVMedicineRENVaccines, Vol 9, Iss 1346, p 1346 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 COVID-19 betacoronavirus vaccine betacoronaviridae TMV Medicine R
spellingShingle	SARS-CoV-2 COVID-19 betacoronavirus vaccine betacoronaviridae TMV Medicine R 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
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.
format	article
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
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_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_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_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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d948abd924354895b2c5b1c46d082bd9
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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

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