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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 233(2021) vom: 15. Dez., Seite 108888
1. Verfasser: Giorgetti, Sofía Inés (VerfasserIn)
Weitere Verfasser: Etcheverrigaray, Marina, Terry, Frances, Martin, William, De Groot, Anne Searls, Ceaglio, Natalia, Oggero, Marcos, Mufarrege, Eduardo Federico
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2021
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Alpha interferon Antiviral therapy COVID-19 De-immunization In silico prediction T cell epitope Antibodies, Neutralizing Antiviral Agents mehr... Interferon-alpha Recombinant Proteins
Beschreibung
Zusammenfassung:Copyright © 2021 Elsevier Inc. All rights reserved.
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
Beschreibung:Date Completed 20.12.2021
Date Revised 21.12.2022
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2021.108888