Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection

Carlos Ávila-Nieto, Júlia Vergara-Alert, Pep Amengual-Rigo, Erola Ainsua-Enrich, Marco Brustolin, María Luisa Rodríguez de la Concepción, Núria Pedreño-Lopez, Jordi Rodon, Victor Urrea, Edwards Pradenas, Silvia Marfil, Ester Ballana, Eva Riveira-Muñoz, Mònica Pérez, Núria Roca, Ferran Tarrés-Freixas, Guillermo Cantero, Anna Pons-Grífols, Carla Rovirosa, Carmen Aguilar-Gurrieri, Raquel Ortiz, Ana Barajas, Benjamin Trinité, Rosalba Lepore, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Nuria Izquierdo-Useros, Alfonso Valencia, Julià Blanco, Victor Guallar, Bonaventura Clotet, Joaquim Segalés () and Jorge Carrillo ()
Additional contact information
Carlos Ávila-Nieto: Campus Can Ruti
Júlia Vergara-Alert: Campus de la Universitat Autònoma de Barcelona (UAB)
Pep Amengual-Rigo: Barcelona Supercomputing Center (BSC)
Erola Ainsua-Enrich: Campus Can Ruti
Marco Brustolin: Campus de la Universitat Autònoma de Barcelona (UAB)
María Luisa Rodríguez de la Concepción: Campus Can Ruti
Núria Pedreño-Lopez: Campus Can Ruti
Jordi Rodon: Campus de la Universitat Autònoma de Barcelona (UAB)
Victor Urrea: Campus Can Ruti
Edwards Pradenas: Campus Can Ruti
Silvia Marfil: Campus Can Ruti
Ester Ballana: Campus Can Ruti
Eva Riveira-Muñoz: Campus Can Ruti
Mònica Pérez: Campus de la Universitat Autònoma de Barcelona (UAB)
Núria Roca: Campus de la Universitat Autònoma de Barcelona (UAB)
Ferran Tarrés-Freixas: Campus Can Ruti
Guillermo Cantero: Campus de la Universitat Autònoma de Barcelona (UAB)
Anna Pons-Grífols: Campus Can Ruti
Carla Rovirosa: Campus Can Ruti
Carmen Aguilar-Gurrieri: Campus Can Ruti
Raquel Ortiz: Campus Can Ruti
Ana Barajas: Campus Can Ruti
Benjamin Trinité: Campus Can Ruti
Rosalba Lepore: Barcelona Supercomputing Center (BSC)
Jordana Muñoz-Basagoiti: Campus Can Ruti
Daniel Perez-Zsolt: Campus Can Ruti
Nuria Izquierdo-Useros: Campus Can Ruti
Alfonso Valencia: Barcelona Supercomputing Center (BSC)
Julià Blanco: Campus Can Ruti
Victor Guallar: Barcelona Supercomputing Center (BSC)
Bonaventura Clotet: Campus Can Ruti
Joaquim Segalés: Campus de la Universitat Autònoma de Barcelona (UAB)
Jorge Carrillo: Campus Can Ruti

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.

Date: 2024
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DOI: 10.1038/s41467-024-46714-w

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