PreprintCited by 28SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studiesvaccines and immunoinformatics approaches

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

Open access
Barreiro, Antonio, Prenafeta, Antoni, Bech-Sabat, Gregori, Roca, Mercè, Mur, Eva Perozo, March, Ricard, González-González, Luis, Madrenas, Laia, Corominas, Júlia, Fernández, Alex, Moros, Alexandra, Cañete, Manuel, Molas, Mercè, Pentinat-Pelegrin, Thais, Panosa, Clara, Moreno, Alberto, Molas, Ester Puigvert, Vilarrassa, Eva Pol, Palmada, Jordi, Garriga, Carme, Cabañas, Teresa Prat, Iglesias-Fernández, Javier, Vergara-Alert, Júlia, Lorca-Oró, Cristina, Roca, Núria, Fernández-Bastit, Leira, Rodon, Jordi, Pérez, Mònica, Segalés, Joaquim, Pradenas, Edwards, Marfil, Silvia, Trinité, Benjamin, Ortiz, Raquel, Clotet, Bonaventura, Blanco, Julià, Pedroza, Jorge Díaz, Carrasco, Rosa Ampudia, Salgado, Yaiza Rosales, Loubat-Casanovas, Jordina, Larripa, Sara Capdevila, Prado, Julia Garcia, Barretina, Jordi, Sisteré-Oró, Marta, Rica, Paula Cebollada, Meyerhans, Andreas, Ferrer, Laura·2021·iScience

Preprint — published as 10.1016/j.isci.2023.106126 · Paper page

Abstract

Summary: Current C0VID-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 neutralising 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.

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Metadata

Authors
Barreiro, A., Prenafeta, A., Bech-Sabat, G., Roca, M., Mur, E. P., March, R., González-González, L., Madrenas, L., Corominas, J., Fernández, A., Moros, A., Cañete, M., Molas, M., Pentinat-Pelegrin, T., Panosa, C., Moreno, A., Molas, E. P., Vilarrassa, E. P., Palmada, J., Garriga, C., Cabañas, T. P., Iglesias-Fernández, J., Vergara-Alert, J., Lorca-Oró, C., Roca, N., Fernández-Bastit, L., Rodon, J., Pérez, M., Segalés, J., Pradenas, E., Marfil, S., Trinité, B., Ortiz, R., Clotet, B., Blanco, J., Pedroza, J. D., Carrasco, R. A., Salgado, Y. R., Loubat-Casanovas, J., Larripa, S. C., Prado, J. G., Barretina, J., Sisteré-Oró, M., Rica, P. C., Meyerhans, A., & Ferrer, L.
Affiliations
  • Universitat Autònoma de Barcelona (ES)
  • Universitat de Vic - Universitat Central de Catalunya (ES)
  • Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
  • Universitat Pompeu Fabra (ES)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
Corresponding author
  • Barreiro, Antonio
  • Prenafeta, Antoni
Venue
iScience
Publisher
openRxiv
Published
2021-11-23
Volume
26
Issue
3
Pages
106126-106126
ISSN
2589-0042 (ISSN-L)
OpenAlex
W4318955566
Cited by
28
References
1
Citations by year
2026: 2 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 3
FWCI
5.17
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IRTA (Institut de Recerca i Tecnologia Agroalimentaries) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
COVID-19 vaccines, SARS-CoV-2, receptor binding domain, recombinant protein vaccine, oil-in-water emulsions, prime-boost vaccination, K18-hACE2 mice, Beta variant, Alpha variant, Omicron variant, Delta variant, neutralizing antibodies, T cell response, vaccine efficacy, vaccine tolerability

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