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oai:recercat.cat:20.500.12327/27232026-03-07T00:33:45Zcom_2072_4428com_2072_4427col_2072_487898

urn:hdl:20.500.12327/2723 Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant 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 Producció Animal Sanitat Animal 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. 2023-12-04 info:eu-repo/semantics/article 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. 1664-3224 http://hdl.handle.net/20.500.12327/2723 https://doi.org/10.3389/fimmu.2023.1291972 eng Frontiers in Immunology 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/ 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/ 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/ EU/HE/101046118/EC/RBD Dimer recombinant protein vaccine against SARSCoV2/RBDCOV http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Attribution 4.0 International Frontiers Media