Direct cloning of novel and specific human neutralizing anti-interferon-alpha or anti-interferon-beta antibodies

Background: Type I interferons (IFNs) play a pivotal role in the development of immune responses and have significant clinical importance. However, dysregulated activation of type-I IFN response has been associated with a wide range of disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action, enabling the development of more effective therapeutic strategies.

Methods: We identified, cloned, and characterized by enzyme-linked immunosorbent assay (ELISA), IFN receptor dimerization assay, signal transducer and activator of transcription 1 (STAT-1) phosphorylation, surface plasmon resonance, and western blot the binding/neutralizing/specificity properties of novel human anti-IFN-α and IFN-β monoclonal antibodies (Abs). The Abs were sourced from individuals with multiple sclerosis with a history or ongoing IFN-β therapy, and from antiretroviral therapy (ART)-suppressed individuals with chronic HIV-1 infection who had been treated with IFN-α.

Results: We observed that clones AH07856, and AH07857 effectively neutralize IFN-α-mediated IFN receptor dimerization and signaling but not IFN-β. Likewise, clones AH07859, and AH07866, neutralize IFN-β-mediated IFN receptor dimerization and signaling but not IFN-α.

Conclusion: We describe novel neutralizing Abs that selectively block human IFN-α or IFN-β with potential applications in research, and in therapeutics and other medical interventions.