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| Home > Articles > Published articles > Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant |
| Home > Articles > Published articles > Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant |
(Universitat Autònoma de Barcelona. Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal) (IrsiCaixa) (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal) (IrsiCaixa) (IrsiCaixa) (Universitat Autònoma de Barcelona. Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (Centro de Investigación Biomédica en Red de Enfermedades Infecciosas) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (IrsiCaixa) (Centro de Investigación Biomédica en Red de Enfermedades Infecciosas) (Institució Catalana de Recerca i Estudis Avançats) (Universitat de Vic - Universitat Central de Catalunya) (Fundació Lluita contra les Infeccions) (Institució Catalana de Recerca i Estudis Avançats) (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals) (IrsiCaixa)
| Date: | 2023 |
| 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. |
| Grants: | Instituto de Salud Carlos III PI17/01518 Instituto de Salud Carlos III PI18/01332 Agencia Estatal de Investigación PID2020-117145RB-I00 European Commission 101046118 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | COVID-19 ; SARS-CoV-2 ; Vaccine ; Neutralizing antibodies ; Humoral response ; Spike glycoprotein |
| Published in: | Frontiers in immunology, Vol. 14 (december 2023) , ISSN 1664-3224 |
