Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2

Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here,...

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Autores: Barreiro, Antonio, Sisteré-Oró, Marta, Cebollada Rica, Paula, Meyerhans, Andreas, Ferrer, Laura
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/56976
Acceso en línea:http://hdl.handle.net/10230/56976
http://dx.doi.org/10.1016/j.isci.2023.106126
Access Level:acceso abierto
Palabra clave:Health sciences
Immune response
Immunology
Microbiology
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spelling Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2Barreiro, AntonioSisteré-Oró, MartaCebollada Rica, PaulaMeyerhans, AndreasFerrer, LauraHealth sciencesImmune responseImmunologyMicrobiologyCurrent COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.This project was partially funded by the Center for the Development of Industrial Technology (CDTI, IDI20210115), a public organization answering to the Spanish Ministry of Science and Innovation. Javier Iglesias-Fernández is supported by the Torres Quevedo Programme grant no. PTQ2020-011291 by the Spanish Ministry of Science and Innovation.Elsevier202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/56976http://dx.doi.org/10.1016/j.isci.2023.106126reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésiScience. 2023 Mar 17;26(3):106126info:eu-repo/grantAgreement/ES/2PE/PTQ2020-011291© 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/569762026-06-12T07:21:37Z
dc.title.none.fl_str_mv Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
title Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
spellingShingle Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
Barreiro, Antonio
Health sciences
Immune response
Immunology
Microbiology
title_short Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
title_full Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
title_fullStr Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
title_full_unstemmed Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
title_sort Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
dc.creator.none.fl_str_mv Barreiro, Antonio
Sisteré-Oró, Marta
Cebollada Rica, Paula
Meyerhans, Andreas
Ferrer, Laura
author Barreiro, Antonio
author_facet Barreiro, Antonio
Sisteré-Oró, Marta
Cebollada Rica, Paula
Meyerhans, Andreas
Ferrer, Laura
author_role author
author2 Sisteré-Oró, Marta
Cebollada Rica, Paula
Meyerhans, Andreas
Ferrer, Laura
author2_role author
author
author
author
dc.subject.none.fl_str_mv Health sciences
Immune response
Immunology
Microbiology
topic Health sciences
Immune response
Immunology
Microbiology
description Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4+ and CD8+ T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/56976
http://dx.doi.org/10.1016/j.isci.2023.106126
url http://hdl.handle.net/10230/56976
http://dx.doi.org/10.1016/j.isci.2023.106126
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv iScience. 2023 Mar 17;26(3):106126
info:eu-repo/grantAgreement/ES/2PE/PTQ2020-011291
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
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