Gag Virus-like Particles Functionalized with SARS-CoV-2 Variants: Generation, Characterization and Recognition by COVID-19 Convalescent Patients' Sera
Boix-Besora, Arnau (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Gòdia, Francesc (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)
Cervera Gracia, Laura (Universitat Autònoma de Barcelona. Departament d'Enginyeria Química, Biològica i Ambiental)

Data:	2023
Resum:	The robustness, safety, versatility, and high immunogenicity of virus-like particles (VLPs) make them a promising approach for the generation of vaccines against a broad range of pathogens. VLPs are recombinant macromolecular structures that closely mimic the native conformation of viruses without carrying viral genetic material. Particularly, HIV-1 Gag-based VLPs are a suitable platform for the presentation of the SARS-CoV-2 Spike (S) protein on their surface. In this context, this work studies the effect of different rationally engineered mutations of the S protein to improve some of its characteristics. The studied variants harbored mutations such as proline substitutions for S stabilization, D614G from the early dominant pandemic form, the elimination of the S1/S2 furin cleavage site to improve S homogeneity, the suppression of a retention motif to favor its membrane localization, and cysteine substitutions to increase its immunogenicity and avoid potential undesired antibody-dependent enhancement (ADE) effects. The influence of the mutations on VLP expression was studied, as well as their immunogenic potential, by testing the recognition of the generated VLP variants by COVID-19 convalescent patients' sera. The results of this work are conceived to give insights on the selection of S protein candidates for their use as immunogens and to showcase the potential of VLPs as carriers for antigen presentation.
Ajuts:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00143
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	SARS-CoV-2 ; Variants ; Spike ; Virus-like particles ; COVID-19 ; D614G ; Furin cleavage
Publicat a:	Vaccines (Basel), Vol. 11, Issue 11 (October 2023) , art. 1641, ISSN 2076-393X

DOI: 10.3390/vaccines11111641
PMID: 38005972

16 p, 2.4 MB

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