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Nat Commun
. 2024 Mar 21;15(1):2349.
doi: 10.1038/s41467-024-46714-w. Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
Carlos Ávila-Nieto # 1 , Júlia Vergara-Alert # 2 3 , Pep Amengual-Rigo # 4 , Erola Ainsua-Enrich 1 , Marco Brustolin 2 3 5 , María Luisa Rodríguez de la Concepción 1 , Núria Pedreño-Lopez 1 , Jordi Rodon 2 3 , Victor Urrea 1 , Edwards Pradenas 1 , Silvia Marfil 1 , Ester Ballana 1 6 7 , Eva Riveira-Muñoz 1 , Mònica Pérez 2 3 , Núria Roca 2 3 , Ferran Tarrés-Freixas 1 2 3 , Guillermo Cantero 2 , Anna Pons-Grífols 1 , Carla Rovirosa 1 , Carmen Aguilar-Gurrieri 1 , Raquel Ortiz 1 , Ana Barajas 1 , Benjamin Trinité 1 , Rosalba Lepore 4 , Jordana Muñoz-Basagoiti 1 , Daniel Perez-Zsolt 1 , Nuria Izquierdo-Useros 1 6 7 , Alfonso Valencia 4 8 , Julià Blanco 1 6 7 8 , Victor Guallar 4 9 , Bonaventura Clotet 1 6 7 8 10 11 , Joaquim Segalés 12 13 14 , Jorge Carrillo 15 16 17
Affiliations
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.
. 2024 Mar 21;15(1):2349.
doi: 10.1038/s41467-024-46714-w. Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
Carlos Ávila-Nieto # 1 , Júlia Vergara-Alert # 2 3 , Pep Amengual-Rigo # 4 , Erola Ainsua-Enrich 1 , Marco Brustolin 2 3 5 , María Luisa Rodríguez de la Concepción 1 , Núria Pedreño-Lopez 1 , Jordi Rodon 2 3 , Victor Urrea 1 , Edwards Pradenas 1 , Silvia Marfil 1 , Ester Ballana 1 6 7 , Eva Riveira-Muñoz 1 , Mònica Pérez 2 3 , Núria Roca 2 3 , Ferran Tarrés-Freixas 1 2 3 , Guillermo Cantero 2 , Anna Pons-Grífols 1 , Carla Rovirosa 1 , Carmen Aguilar-Gurrieri 1 , Raquel Ortiz 1 , Ana Barajas 1 , Benjamin Trinité 1 , Rosalba Lepore 4 , Jordana Muñoz-Basagoiti 1 , Daniel Perez-Zsolt 1 , Nuria Izquierdo-Useros 1 6 7 , Alfonso Valencia 4 8 , Julià Blanco 1 6 7 8 , Victor Guallar 4 9 , Bonaventura Clotet 1 6 7 8 10 11 , Joaquim Segalés 12 13 14 , Jorge Carrillo 15 16 17
Affiliations
- PMID: 38514609
- PMCID: PMC10957958
- DOI: 10.1038/s41467-024-46714-w
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.