Artículo
A COVID-19 vaccine candidate based on SARS-CoV-2 spike protein and immune-stimulating complexes
Villarraza, Carlos Javier
; Fuselli, Antonela
; Gugliotta, Agustina
; Garay, Ernesto Sergio
; Rodríguez, María Celeste
; Fontana, Diego Sebastian
; Antuña, Sebastián; Gastaldi, Victoria
; Battagliotti, Juan Manuel
; Tardivo, María Belén; Alvarez, Diego Ezequiel
; Castro, Eliana Florencia
; Cassataro, Juliana
; Ceaglio, Natalia Analia
; Prieto, Claudio
Fecha de publicación:
06/2023
Editorial:
Springer
Revista:
Applied Microbiology and Biotechnology
ISSN:
0175-7598
e-ISSN:
1432-0614
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Spike protein form SARS-CoV-2, the etiologic agent of COVID-19 pandemic disease, constitutes a structural protein that proved to be the main responsible for neutralizing antibodies production. Thus, its sequence is highly considered for the design of chimeric proteins that might be used as vaccine candidates. Animal cell culture represents the best option for the production of subunit vaccines based on recombinant proteins since they introduce post-translational modifications that are important to mimic the natural antigenic epitopes. Particularly, the human cell line HEK293T has been explored and used for the production of biotherapeutics since the products derived from them present human-like post translational modifications that are important for the protein´s activity and immunogenicity. In this work, the spike ectodomain (S-ED) was produced in sHEK293T cells using a 1 L stirred tank bioreactor operated in perfusion mode. Harvests were purified and S-ED characterization was performed, revealing the expected size and morphology. High N-glycans content was confirmed. Furthermore, S-ED specific binding with the hACE2 (human Angiotensin Converting Enzyme 2) receptor could be verified Two different adjuvants were used to evaluate the immunogenicity of S-ED: the traditional aluminium hydroxide and immune-stimulating complexes (ISCOMs). Both formulations demonstrated the presence of anti-RBD antibodies in the plasma of immunized mice, being significantly higher for the latter adjuvant. Also, higher levels of IFN-γ and IL-4 were detected after the ex vivo immune stimulation of spleen-derived MNCs from ISCOMs immunized mice. Further analysis confirmed that S-ED/ISCOMs elicits neutralizing antibodies against SARS CoV-2.
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Identificadores
Colecciones
Articulos (IIBIO)
Articulos de INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Articulos(CCT - SANTA FE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Citación
Villarraza, Carlos Javier; Fuselli, Antonela; Gugliotta, Agustina; Garay, Ernesto Sergio; Rodríguez, María Celeste; et al.; A COVID-19 vaccine candidate based on SARS-CoV-2 spike protein and immune-stimulating complexes; Springer; Applied Microbiology and Biotechnology; 107; 11; 6-2023; 3429-3441
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