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

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARSCoV-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. H...

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Bibliographic Details
Authors: Ávila-Nieto, Carlos, Serra Gironella, Joan, Amengual-Rigo, Pep, Ainsua-Enrich, Erola, Brustolin, Marco, Rodríguez de la Concepción, María Luisa, Pedreño-Lopez, Núria, Rodon, Jordi, Urrea, Victor, Pradenas, Edwards, Marfil, Silvia, Ballana, Ester, Riveira-Muñoz, Eva, Pérez, Mònica, Roca, Núria, Tarrés-Freixas, Ferran, Cantero, Guillermo, Pons-Grífols, Anna, Rovirosa, Carla, Aguilar-Gurrieri, Carmen, Ortiz, Raquel, Barajas, Ana, Trinité, Benjamin, Lepore, Rosalba, Muñoz-Basagoiti, Jordana, Perez-Zsolt, Daniel, Izquierdo-Useros, Nuria, Valencia, Alfonso, Blanco, Julià, Guallar, Victor, Clotet, Bonaventura, Segalés, Joaquim, Carrillo, Jorge
Format: article
Publication Date:2024
Country:España
Institution:Institut de Recerca i Tecnologia Agroalimentàries (IRTA)
Repository:IRTA Pubpro. Open Digital Archive
OAI Identifier:oai:repositori.irta.cat:20.500.12327/2917
Online Access:http://hdl.handle.net/20.500.12327/2917
https://doi.org/10.1038/s41467-024-46714-w
Access Level:Open access
Keyword:619
Description
Summary:Safe and effective severe acute respiratory syndrome coronavirus 2 (SARSCoV-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.

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