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Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant
dc.contributor.author | Ávila-Nieto, Carlos | |
dc.contributor.author | Vergara-Alert, Júlia | |
dc.contributor.author | Amengual-Rigo, Pep | |
dc.contributor.author | Ainsua-Enrich, Erola | |
dc.contributor.author | Brustolin, Marco | |
dc.contributor.author | Rodríguez de la Concepción, María Luisa | |
dc.contributor.author | Pedreño-Lopez, Núria | |
dc.contributor.author | Rodon, Jordi | |
dc.contributor.author | Urrea, Victor | |
dc.contributor.author | Pradenas, Edwards | |
dc.contributor.author | Marfil, Silvia | |
dc.contributor.author | Ballana, Ester | |
dc.contributor.author | Riveira-Muñoz, Eva | |
dc.contributor.author | Pérez, Mònica | |
dc.contributor.author | Roca, Núria | |
dc.contributor.author | Tarrés-Freixas, Ferran | |
dc.contributor.author | Carabelli, Julieta | |
dc.contributor.author | Cantero, Guillermo | |
dc.contributor.author | Pons-Grífols, Anna | |
dc.contributor.author | Rovirosa, Carla | |
dc.contributor.author | Aguilar-Gurrieri, Carmen | |
dc.contributor.author | Ortiz, Raquel | |
dc.contributor.author | Barajas, Ana | |
dc.contributor.author | Trinité, Benjamin | |
dc.contributor.author | Lepore, Rosalba | |
dc.contributor.author | Muñoz-Basagoiti, Jordana | |
dc.contributor.author | Perez-Zsolt, Daniel | |
dc.contributor.author | Izquierdo-Useros, Nuria | |
dc.contributor.author | Valencia, Alfonso | |
dc.contributor.author | Blanco, Julià | |
dc.contributor.author | Clotet, Bonaventura | |
dc.contributor.author | Guallar, Victor | |
dc.contributor.author | Segalés, Joaquim | |
dc.contributor.author | Carrillo, Jorge | |
dc.contributor.other | Producció Animal | ca |
dc.date.accessioned | 2024-01-17T16:16:14Z | |
dc.date.available | 2024-01-17T16:16:14Z | |
dc.date.issued | 2023-12-04 | |
dc.identifier.citation | Ávila‐Nieto, Carlos, Júlia Vergara‐Alert, Pep Amengual-Rigo, Erola Ainsua-Enrich, Marco Brustolin, Maria Luisa Rodrı́guez De La Concepción, and Núria Pedreño-López, et al. 2023. “Novel spike-stabilized trimers with improved production protect K18-HACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-COV-2 beta variant”. Frontiers in Immunology 14: 1291972. doi: 10.3389/fimmu.2023.1291972. | ca |
dc.identifier.issn | 1664-3224 | ca |
dc.identifier.uri | http://hdl.handle.net/20.500.12327/2723 | |
dc.description.abstract | 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. | ca |
dc.description.sponsorship | The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Grifols pharmaceutical, the CERCA Program (2021 SGR 00452; Generalitat de Catalunya), Direcció General de Recerca i Innovació en Salut (Generalitat de Catalunya) (projects SLD0015 and SLD0016), the Carlos III Health Institute (PI17/01518 and PI18/01332), and the crowdfunding projects “YomeCorono”, BonPreu/ Esclat, and Correos. JB is supported by the Health Department of the Catalan Government (Generalitat de Catalunya). CÁ-N, AP-G, and PA-R were supported by predoctoral grants from Generalitat de Catalunya and Fons Social Europeu (2020 FI_B_0742; 2022 FI_B_00698 and 2020FI_B2_00138, respectively). EP was supported by a doctoral grant from National Agency for Research and Development of Chile (ANID: 72180406). NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118). This study was also supported by CIBER - Consorcio Centro de Investigación Biomédica en Red (CB 2021), Carlos III Health Institute, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. | ca |
dc.format.extent | 14 | ca |
dc.language.iso | eng | ca |
dc.publisher | Frontiers Media | ca |
dc.relation.ispartof | Frontiers in Immunology | ca |
dc.rights | Attribution 4.0 International | ca |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant | ca |
dc.type | info:eu-repo/semantics/article | ca |
dc.description.version | info:eu-repo/semantics/publishedVersion | ca |
dc.rights.accessLevel | info:eu-repo/semantics/openAccess | |
dc.embargo.terms | cap | ca |
dc.relation.projectID | ISCII/Programa Estatal de fomento de la investigación científica y técnica de excelencia/PI17-01518/ES/Desarrollo de una plataforma de vacunas contra el VIH basada en partículas similares a virus (VLP) envueltas y de alta densidad antigénica/ | ca |
dc.relation.projectID | ISCII/Programa Estatal de fomento de la investigación científica y técnica de excelencia/PI18-01332/ES/Identificación, aislamiento y caracterización de anticuerpos que interfieren con la acción de los anticuerpos neutralizantes en personas infectadas por el virus de la inmunodeficiencia humana/ | ca |
dc.relation.projectID | MICINN/Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-117145RB-I00/ES/NUEVAS TERAPIAS ANTIVIRALES E INMUNOMODULADORAS FRENTE AL SARS-COV-2/ | ca |
dc.relation.projectID | EU/H2020/101046118/EC/RBD Dimer recombinant protein vaccine against SARSCoV2/RBDCOV | ca |
dc.subject.udc | 619 | ca |
dc.identifier.doi | https://doi.org/10.3389/fimmu.2023.1291972 | ca |
dc.contributor.group | Sanitat Animal | ca |
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