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 (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....

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Autores: Avila-Nieto, Carlos, Vergara-Alert, Júlia|||0000-0001-7484-444X, Amengual-Rigo, Pep, Ainsua-Enrich, Erola|||0000-0001-7901-5798, Brustolin, Marco|||0000-0002-3594-4488, Rodriguez de la Concepción, Maria Luisa|||0000-0002-6944-3462, Pedreño López, Núria|||0000-0001-6927-2301, Rodon, Jordi|||0000-0002-1032-9091, Urrea, Víctor|||0000-0002-2577-856X, Pradenas, Edwards|||0000-0001-5162-8920, Marfil, Sílvia|||0000-0003-0139-5000, Ballana, Ester|||0000-0002-5215-7363, Riveira Muñoz, Eva|||0000-0002-6396-1162, Pérez, Mònica, Roca, Núria, Tarrés-Freixas, Ferran|||0000-0002-1569-0126, Cantero, Guillermo|||0000-0003-4200-503X, Pons-Grífols, Anna|||0000-0002-8402-3941, Rovirosa, Carla|||0000-0002-7111-0253, Aguilar-Gurrieri, Carmen|||0000-0002-5701-7650, Ortiz, Raquel|||0000-0002-6919-2026, Barajas Vélez, Ana|||0000-0003-1103-9499, Trinité, Benjamin|||0000-0003-3809-042X, Lepore, Rosalba, Muñoz-Basagoiti, Jordana|||0000-0002-0384-5928, Perez-Zsolt, Daniel|||0000-0003-4192-7622, Izquierdo Useros, Nuria|||0000-0002-1039-1821, Valencia, Alfonso|||0000-0002-8937-6789, Blanco, Julià|||0000-0002-2225-0217, Guallar, Victor|||0000-0002-4580-1114, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Segalés Coma, Joaquim|||0000-0002-1539-7261, Carrillo, Jorge|||0000-0003-0221-5948
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:291293
Acceso en línea:https://ddd.uab.cat/record/291293
https://dx.doi.org/urn:doi:10.1038/s41467-024-46714-w
Access Level:acceso abierto
Palabra clave:Viral infection
Protein vaccines
Descripción
Sumario: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. In this study, the authors report a mutation that increases the production of recombinant SARS-CoV-2 Spike and exposure of the RBD. In animal models, a Spike-based vaccine containing the mutation induces strong immunogenicity, provides protection from disease and results in faster tissue viral clearance.

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