iScience (Mar 2023)

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

  • Antonio Barreiro,
  • Antoni Prenafeta,
  • Gregori Bech-Sabat,
  • 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,
  • Joaquim Segalés,
  • Edwards Pradenas,
  • Silvia Marfil,
  • Benjamin Trinité,
  • Raquel Ortiz,
  • Bonaventura Clotet,
  • Julià Blanco,
  • Jorge Díaz Pedroza,
  • Rosa Ampudia Carrasco,
  • Yaiza Rosales Salgado,
  • Jordina Loubat-Casanovas,
  • Sara Capdevila Larripa,
  • Julia Garcia Prado,
  • Jordi Barretina,
  • Marta Sisteré-Oró,
  • Paula Cebollada Rica,
  • Andreas Meyerhans,
  • Laura Ferrer

Journal volume & issue
Vol. 26, no. 3
p. 106126

Abstract

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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.

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