Humanized Murine Monoclonal Antibodies That Neutralize Type-1 Interferon (IFN) Activity

Interferons (IFNs) are a family of cytokines that function in response to an immune challenge such as a viral or bacterial infection. Type I IFNs are produced by immune cells (predominantly monocytes and dendritic cells) as well as fibroblasts and signal through a specific cell surface receptor complex (IFNAR) that consist of IFNAR1 and IFNAR2 chains. Type-I IFNs exert several common effects including antiviral, antiproliferative, and immunomodulatory activities. However, Type I IFNs also have pro-inflammatory effects, especially in the presence of TNF-a. Therefore, neutralizing the proinflammatory effect of Type I interferon could have wide clinical applications in autoimmune diseases like SLE, or in acute and chronic viral diseases like SARS–CoV–2, HIV or HCV infection, respectively, in which IFN-induced inflammation may be detrimental.

Scientists at the National Institute of Allergy and Infectious Diseases (NIAID) have developed two anti-IFN receptor 2 (IFNAR2) antibodies, B7 and A10, that are effective in vitro at neutralizing Type I IFN activities. The antibodies are comprised of two heavy chains and two light chains of amino acids. Both antibodies are able to bind to the extracellular domain of IFNAR2, Type I IFN receptor subunit 2, thus suppressing IFN signaling.

Because there are no potent IFNAR2 antibodies for therapies commercially available at this time, these antibodies are a novel therapeutic tool that could be used exclusively or in combination to treat chronic inflammatory diseases (like autoimmune disorders such as SLE) in which sustained IFN production may lead to both systemic and specific organ dysfunctions or chronic viral diseases (such as HIV, HCV) in which sustained IFN production has deleterious effects on immunologic function.