Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations...

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Detalles Bibliográficos
Autores: 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, Carabelli, Julieta, 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, Clotet, Bonaventura, Guallar, Victor, Segalés, Joaquim, Carrillo, Jorge
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:20.500.12327/2723
Acceso en línea:http://hdl.handle.net/20.500.12327/2723
https://doi.org/10.3389/fimmu.2023.1291972
Access Level:acceso abierto
Palabra clave:619
Descripción
Sumario:Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S- 29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.

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