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

• Published in: JHEP reports Vol. 3; no. 6; p. 100361
• Main Authors: Ma, Haiyan, Lim, Tien Huey, Leerapun, Apinya, Weltman, Martin, Jia, Jidong, Lim, Young-suk, Tangkijvanich, Pisit, Sukeepaisarnjaroen, Wattana, Ji, Yun, Le Bert, Nina, Li, Dong, Zhang, Yao, Hamatake, Robert, Tan, Nicole, Li, Chunming, Strasser, Simone I., Ding, Huiguo, Yoon, Jung-Hwan, Stace, Nigel H., Ahmed, Tanvir, Anderson, Dave E., Yan, Li, Bertoletti, Antonio, Zhu, Qing, Yuen, Man-Fung
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2021; Elsevier
• Subjects: BRII-179; CHB; Gastroenterology and Hepatology; HBV-specific immune response; IFN-alpha; immunotherapy; AE; IM; Anti-HBs; HBeAg; PEG-IFN-α; ALT; HBsAg; IU; IFN-alpha; PBMCs; BRII-179; ELISpot; HBV-specific immune response; IFN-α; NA; SAE; immunotherapy; CHB; Th1; HBV; BMI; interferon-α; hepatitis B virus; alanine aminotransferase; intramuscular; hepatitis B e antigen; pegylated interferon-α; chronic hepatitis B; peripheral blood mononuclear cells; serious adverse events; international units; nucleos(t)ide analogue; hepatitis B surface antigen; body mass index; adverse event; hepatitis B surface antibody; T helper type 1; enzyme-linked immune absorbent spot; ALT, alanine aminotransferase; HBV, hepatitis B virus; HBeAg, hepatitis B e antigen; CHB, chronic hepatitis B; NA, nucleos(t)ide analogue; HBsAg, hepatitis B surface antigen; Th1, T helper type 1; BMI, body mass index; IM, intramuscular; IU, international units; AE, adverse event; IFN-α, interferon-α; Anti-HBs, hepatitis B surface antibody; ELISpot, enzyme-linked immune absorbent spot; PEG-IFN-α, pegylated interferon-α; SAE, serious adverse events; PBMCs, peripheral blood mononuclear cells
• ISSN: 2589-5559; 2589-5559
• DOI: 10.1016/j.jhepr.2021.100361

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. 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. 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 majority of treated patients. Overall, no notable reduction of HBsAg was observed after BRII-179 treatment. In patients with CHB under NA therapy, BRII-179 with/without IFN-α exhibited a good safety profile and induced HBV-specific B- and T-cell immune responses. These data support further clinical evaluation of BRII-179 in combination with other therapies. ACTRN12619001210167 BRII-179 is a therapeutic vaccine designed to improve the immune response in patients with chronic hepatitis B. In this study, BRII-179 alone or with a low dose of interferon-α was safe, well tolerated, and induced enhanced HBV-specific antibody and T-cell responses in patients with chronic hepatitis B. However, BRII-179 treatment alone had minimal effect on patient’s virological status. The potential of BRII-179 to achieve a functional cure in conjunction with other agents is being evaluated in the clinic. [Display omitted] •BRII-179 admixed with or without IFN-α is safe and well tolerated.•BRII-179 can induce antigen-specific humoral and T-cell responses in patients with CHB.•BRII-179-induced immune responses were insufficient to reduce serum HBsAg in virally suppressed patients.•These data support the further clinical evaluation of BRII-179, especially in combination with other therapies.