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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Published in:iScience Vol. 26; no. 3; p. 106126
Main Authors: Barreiro, Antonio, Prenafeta, Antoni, Bech-Sabat, Gregori, Roca, Mercè, Perozo Mur, Eva, March, Ricard, González-González, Luis, Madrenas, Laia, Corominas, Júlia, Fernández, Alex, Moros, Alexandra, Cañete, Manuel, Molas, Mercè, Pentinat-Pelegrin, Thais, Panosa, Clara, Moreno, Alberto, Puigvert Molas, Ester, Pol Vilarrassa, Eva, Palmada, Jordi, Garriga, Carme, Prat Cabañas, Teresa, 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, Díaz Pedroza, Jorge, Ampudia Carrasco, Rosa, Rosales Salgado, Yaiza, Loubat-Casanovas, Jordina, Capdevila Larripa, Sara, Prado, Julia Garcia, Barretina, Jordi, Sisteré-Oró, Marta, Cebollada Rica, Paula, Meyerhans, Andreas, Ferrer, Laura
Format: Journal Article
Language:English
Published: United States Elsevier Inc 17-03-2023
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Summary: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. [Display omitted] •An RBD-based recombinant protein vaccine (PHH-1V) against COVID-19 has been generated•PHH-1V elicits humoral and cellular responses against different SARS-CoV-2 variants•PHH-1V vaccination prevents mortality in SARS-CoV-2 infected K18-hACE2 mice•PHH-1V vaccination reduces Beta, Delta and Omicron infection in lower respiratory airways Health sciences; Immune response; Immunology; Microbiology
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These authors contributed equally.
Lead contact: antoni.prenafeta@hipra.com
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.106126