Nguyen, H. O.; Recordon-Pinson, P.; Andreola, M.-L.; Papagno, L.; Appay, V.

The type-I interferon family is well known for its critical role in innate immunity. It comprises several members, among which IFN-2 and IFN-{beta} are the most extensively studied, with important antiviral and immune-modulatory functions. Recent findings linking autoantibodies against type-I interferons to severe COVID-19 suggest a potential role for IFN-{omega} in combating SARS-CoV-2 infection. However, little is known about human IFN-{omega}, as most research on this interferon has been conducted in feline models. Here, we demonstrate that human IFN-{omega} is secreted at levels comparable to those of IFN-2 or IFN-{beta} upon stimulation with inflammatory agonists, and triggers a robust antiviral response, inhibiting SARS-CoV-2 infection in vitro. Moreover, IFN-{omega} enhances the effector functions of antigen-specific CD8+ T cells primed de novo from healthy donor cells, highlighting its capacity to promote strong cellular immunity. Our results position IFN-{omega} as a key member of the type-I interferon family, with promising potential for therapeutic and vaccine applications.