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Artículo

Development of highly stable and de-immunized versions of recombinant alpha interferon: promising candidates for the treatment of chronic and emerging viral diseases

Giorgetti, Sofia InésIcon ; Etcheverrigaray, MarinaIcon ; Terry, Frances; Martin, William; De Groot, Anne Searls; Ceaglio, Natalia AnaliaIcon ; Oggero Eberhardt, Marcos RafaelIcon ; Mufarrege, Eduardo FedericoIcon
Fecha de publicación: 12/2021
Editorial: Elsevier
Revista: Clinical Immunology
ISSN: 1521-6616
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Biotecnologías de la Salud

Resumen

Human interferon alpha (hIFN-α) administration constitutes the current FDA approved therapy for chronic Hepatitis B and C virus infections. Additionally, hIFN-α treatment efficacy was recently demonstrated in patients with COVID-19. Thus, hIFN-α constitutes a therapeutic alternative for those countries where vaccination is inaccessible and for people who did not respond effectively to vaccination. However, hIFN-α2b exhibits a short plasma half-life resulting in the occurrence of severe side effects. To optimize the cytokine's pharmacokinetic profile, we developed a hyperglycosylated IFN, referred to as GMOP-IFN. Given the significant number of reports showing neutralizing antibodies (NAb) formation after hIFN-α administration, here we applied the DeFT (De-immunization of Functional Therapeutics) approach to develop functional, de-immunized versions of GMOP-IFN. Two GMOP-IFN variants exhibited significantly reduced ex vivo immunogenicity and null antiproliferative activity, while preserving antiviral function. The results obtained in this work indicate that the new de-immunized GMOP-IFN variants constitute promising candidates for antiviral therapy.
Palabras clave: ALPHA INTERFERON , ANTIVIRAL THERAPY , COVID-19 , DE-IMMUNIZATION , IN SILICO PREDICTION , T CELL EPITOPE
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/164831
URL: https://www.sciencedirect.com/science/article/pii/S1521661621002254
DOI: http://dx.doi.org/10.1016/j.clim.2021.108888
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Articulos(CCT - SANTA FE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Citación
Giorgetti, Sofia Inés; Etcheverrigaray, Marina; Terry, Frances; Martin, William; De Groot, Anne Searls ; et al.; Development of highly stable and de-immunized versions of recombinant alpha interferon: promising candidates for the treatment of chronic and emerging viral diseases; Elsevier; Clinical Immunology; 233; 12-2021; 1-12
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