| Autor: |
Carlos Ávila-Nieto, Júlia Vergara-Alert, Pep Amengual-Rigo, Erola Ainsua-Enrich, Marco Brustolin, María Luisa Rodríguez de la Concepción, Núria Pedreño-Lopez, Jordi Rodon, Victor Urrea, Edwards Pradenas, Silvia Marfil, Ester Ballana, Eva Riveira-Muñoz, Mònica Pérez, Núria Roca, Ferran Tarrés-Freixas, Julieta Carabelli, Guillermo Cantero, Anna Pons-Grífols, Carla Rovirosa, Carmen Aguilar-Gurrieri, Raquel Ortiz, Ana Barajas, Benjamin Trinité, Rosalba Lepore, Jordana Muñoz-Basagoiti, Daniel Perez-Zsolt, Nuria Izquierdo-Useros, Alfonso Valencia, Julià Blanco, Bonaventura Clotet, Victor Guallar, Joaquim Segalés, Jorge Carrillo |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2023.1291972 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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