Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle

Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a huma...

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Autores principales:	Joshua M. Royal, Carrie A. Simpson, Alison A. McCormick, Amanda Phillips, Steve Hume, Josh Morton, John Shepherd, Youngjun Oh, Kelsi Swope, Jennifer L. DeBeauchamp, Richard J. Webby, Robert W. Cross, Viktoriya Borisevich, Thomas W. Geisbert, Jennifer K. Demarco, Barry Bratcher, Hugh Haydon, Gregory P. Pogue
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 vaccine nanoparticle receptor-binding domain plant-based manufacturing Medicine R
Acceso en línea:	https://doaj.org/article/43b61c27594a4cee8b9a7611a625c5e8
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spelling	oai:doaj.org-article:43b61c27594a4cee8b9a7611a625c5e82021-11-25T19:11:31ZDevelopment of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle10.3390/vaccines91113472076-393Xhttps://doaj.org/article/43b61c27594a4cee8b9a7611a625c5e82021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1347https://doaj.org/toc/2076-393XStable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.Joshua M. RoyalCarrie A. SimpsonAlison A. McCormickAmanda PhillipsSteve HumeJosh MortonJohn ShepherdYoungjun OhKelsi SwopeJennifer L. DeBeauchampRichard J. WebbyRobert W. CrossViktoriya BorisevichThomas W. GeisbertJennifer K. DemarcoBarry BratcherHugh HaydonGregory P. PogueMDPI AGarticleSARS-CoV-2 vaccinenanoparticlereceptor-binding domainplant-based manufacturingMedicineRENVaccines, Vol 9, Iss 1347, p 1347 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 vaccine nanoparticle receptor-binding domain plant-based manufacturing Medicine R
spellingShingle	SARS-CoV-2 vaccine nanoparticle receptor-binding domain plant-based manufacturing Medicine R Joshua M. Royal Carrie A. Simpson Alison A. McCormick Amanda Phillips Steve Hume Josh Morton John Shepherd Youngjun Oh Kelsi Swope Jennifer L. DeBeauchamp Richard J. Webby Robert W. Cross Viktoriya Borisevich Thomas W. Geisbert Jennifer K. Demarco Barry Bratcher Hugh Haydon Gregory P. Pogue Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
description	Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.
format	article
author	Joshua M. Royal Carrie A. Simpson Alison A. McCormick Amanda Phillips Steve Hume Josh Morton John Shepherd Youngjun Oh Kelsi Swope Jennifer L. DeBeauchamp Richard J. Webby Robert W. Cross Viktoriya Borisevich Thomas W. Geisbert Jennifer K. Demarco Barry Bratcher Hugh Haydon Gregory P. Pogue
author_facet	Joshua M. Royal Carrie A. Simpson Alison A. McCormick Amanda Phillips Steve Hume Josh Morton John Shepherd Youngjun Oh Kelsi Swope Jennifer L. DeBeauchamp Richard J. Webby Robert W. Cross Viktoriya Borisevich Thomas W. Geisbert Jennifer K. Demarco Barry Bratcher Hugh Haydon Gregory P. Pogue
author_sort	Joshua M. Royal
title	Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
title_short	Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
title_full	Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
title_fullStr	Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
title_full_unstemmed	Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
title_sort	development of a sars-cov-2 vaccine candidate using plant-based manufacturing and a tobacco mosaic virus-like nano-particle
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/43b61c27594a4cee8b9a7611a625c5e8
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Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle

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