Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
Open accessPublished version of a preprint
Abstract
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.
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- Authors
- Barreiro, A., Prenafeta, A., Bech-Sabat, G., Roca, M., Perozo Mur, E., March, R., González-González, L., Madrenas, L., Corominas, J., Fernández, A., Moros, A., Cañete, M., Molas, M., Pentinat-Pelegrin, T., Panosa, C., Moreno, A., Puigvert Molas, E., Pol Vilarrassa, E., Palmada, J., Garriga, C., Prat Cabañas, T., 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., Díaz Pedroza, J., Ampudia Carrasco, R., Rosales Salgado, Y., Loubat-Casanovas, J., Capdevila Larripa, S., Prado, J. G., Barretina, J., Sisteré-Oró, M., Cebollada Rica, P., 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)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Barreiro, Antonio
- Prenafeta, Antoni
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2023-03
- Volume
- 26
- Issue
- 3
- Pages
- 106126
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC9893798
- OpenAlex
- W4318955566
- Cited by
- 28
- References
- 8
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 3
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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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