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

GIORGETTI, SOFÍA INÉS; ETCHEVERRIGARAY, MARINA; TERRY, FRANCES; MARTIN, WILLIAM; DE GROOT, ANNE SEARLS; CEAGLIO, NATALIA; OGGERO, MARCOS; MUFARREGE, EDUARDO FEDERICO

CLINICAL IMMUNOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2021 vol. 233

1521-6616

Human interferon alpha (hIFN-α) administration constitutes the current FDA approved therapy for chronicHepatitis 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.