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**pegylated interferon alfa + BRII-179** is an investigational combination regimen being developed for the treatment of chronic hepatitis B virus (HBV) infection. The combination pairs BRII-179 (also known as VBI-2601), a first-in-class recombinant therapeutic vaccine, with pegylated interferon alfa (PEG-IFNα), an approved immunomodulatory cytokine. Originally developed by VBI Vaccines and licensed globally by Brii Biosciences, BRII-179 expresses the Pre-S1, Pre-S2, and S envelope proteins of HBV to break immune tolerance and induce broad, sustained B-cell and T-cell responses. Pegylated interferon alfa acts as an agonist of the type I interferon receptor (IFNAR1/IFNAR2), triggering the JAK-STAT pathway to upregulate interferon-stimulated genes with antiviral and immunomodulatory properties. By combining these complementary mechanisms, the regimen aims to enhance HBV-specific immune responses and increase rates of hepatitis B surface antigen (HBsAg) loss, representing a potential functional cure. The combination has been evaluated in Phase 2 clinical trials, including as an add-on to nucleos(t)ide analogue therapy and in triple-combination regimens with the siRNA elebsiran (BRII-835).
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