Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2
Antonio Barreiro, Antoni Prenafeta, G. Bech-Sàbat, Mercè Roca, Eva Perozo Mur, Ricard March, Luis González‐González, Laia Madrenas, Júlia Corominas, Alex Fernández, Alexandra Moros, Manuel Cañete, Mercè Molas, Thais Pentinat-Pelegrin, Clara Panosa, Alberto Moreno, Ester Puigvert Molas, Eva Pol Vilarrassa, Jordi Palmada, Carme Garriga, Teresa Prat Cabañas, Javier Iglesias‐Fernández, Júlia Vergara‐Alert, Cristina Lorca-Oró, Núria Roca, Leira Fernández‐Bastit, Jordi Rodon, Mònica Pérez, Joaquím Segalés, Edwards Pradenas, Sílvia Marfil, Benjamin Trinité, Raquel Ortiz, Bonaventura Clotet, Julià Blanco, Jorge Díaz Pedroza, Rosa A. Carrasco, Yaiza Rosales Salgado, Jordina Loubat‐Casanovas, Sara Capdevila Larripa, Júlia G. Prado, Jordi Barretina, Marta Sisteré‐Oró, Paula Cebollada Rica, Andreas Meyerhans, Laura Ferrer
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.