Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2.

Barreiro, A.; Prenafeta, A.; Bech-Sabat, G.; Roca, M.; March, R.; Gonzalez, L.; Madrenas, L.; Corominas, J.; Fernandez, A.; Molas, M.; Vergara-Alert, J.; Lorca-Oro, C.; Roca, N.; Fernandez-Bastit, L.; Rodon, J.; Perez, M.; Segales, J.; Pradenas, E.; Marfil, S.; Trinite, B.; Ortiz, R.; Clotet, B.; Blanco, J.; Diaz Pedroza, J.; Ampudia Carrasco, R.; Rosales Salgado, Y.; Loubat Casanovas, J.; Capdevila Larripa, S.; Garcia Prado, J.; Barretina Ginesta, J.; Sistere-Oro, M.; Cebollada Rica, P.; Meyerhans, A.; Ferrer, L.; Torroella, E.

doi:10.1101/2021.11.22.469117

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bioRxiv · 10.1101/2021.11.22.469117

Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2.

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Abstract

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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Barreiro, A., Prenafeta, A., Bech-Sabat, G., Roca, M., March, R., Gonzalez, L., Madrenas, L., Corominas, J., Fernandez, A., Molas, M., Vergara-Alert, J., Lorca-Oro, C., Roca, N., Fernandez-Bastit, L., Rodon, J., Perez, M., Segales, J., Pradenas, E., Marfil, S., Trinite, B., Ortiz, R., Clotet, B., Blanco, J., Diaz Pedroza, J., Ampudia Carrasco, R., Rosales Salgado, Y., Loubat Casanovas, J., Capdevila Larripa, S., Garcia Prado, J., Barretina Ginesta, J., Sistere-Oro, M., Cebollada Rica, P., Meyerhans, A., Ferrer, L., Torroella, E.. 2021-11-23. Preclinical efficacy, safety, and immunogenicity of PHH-1V, a second-generation COVID-19 vaccine candidate based on a novel recombinant RBD fusion heterodimer of SARS-CoV-2.. https://doi.org/10.1101/2021.11.22.469117

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