Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study

作者：Haiyan Ma, Tien Huey Lim, Apinya Leerapun, Martin Weltman, Jidong Jia, Young‐Suk Lim, Pisit Tangkijvanich, Wattana Sukeepaisarnjaroen, Yun Ji, Nina Le Bert, Li Dong, Yao Zhang, Robert Hamatake, Nicole Tan, Chunming Li, Simone I. Strasser, Huiguo Ding, Jung‐Hwan Yoon, N Stace, Tanvir Ahmed, Dave Anderson, Yan Li, Antonio Bertoletti, Qing Zhu, Man‐Fung Yuen · 发表于：JHEP Reports · 年份：2021 · DOI：10.1016/j.jhepr.2021.100361 · 被引用次数：62 · 研究领域：Hepatitis B Virus Studies、Viral Infections and Outbreaks Research、Vibrio bacteria research studies

BACKGROUND & AIMS: Functional cure of chronic HBV infection (CHB) without life-long treatment requires the restoration of defective HBV-specific humoral and cellular immunity. Therapeutic vaccines based on the major structural and non-structural proteins have been tested in patients with CHB but have shown scarce immunogenicity. BRII-179, also known as VBI-2601, is a novel formulation comprised of all 3 HBV surface envelope proteins (Pre-S1, Pre-S2, and S). Safety, antiviral activity, and immunogenicity of BRII-179 admixed with co-adjuvant interferon (IFN)-α were assessed in patients with CHB. METHOD: This randomized, open-label, controlled phase Ib/IIa study included 2 dose levels, 20 μg BRII-179 (Part 1, n = 25) and 40 μg BRII-179 (Part 2, n = 24). Patients, virally suppressed under nucleos(t)ide analogue (NA) therapy were randomized 1:2:2 into 3 cohorts in Part 1 and 1:1 into 2 cohorts in Part 2 to receive 4 monthly intramuscular injections of BRII-179 admixed with/without 3 MIU IFN-α. Antibody and cellular responses to HBsAg, as well as evolution of circulating HBsAg were monitored. RESULTS: Both 20 μg and 40 μg BRII-179 with/without IFN-α were well tolerated with no severe adverse events. BRII-179 induced anti-HBs responses in >30% patients in all treatment cohorts, however, moderate anti-Pre-S1 or anti-Pre-S2 antibody responses were only observed in patients receiving BRII-179 with IFN-α. BRII-179 also restored S-, Pre-S1-, Pre-S2-specific IFN-γ-producing T-cells in the...