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

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...

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Autores principales:	Haiyan Ma, Tien Huey Lim, Apinya Leerapun, Martin Weltman, Jidong Jia, Young-suk Lim, Pisit Tangkijvanich, Wattana Sukeepaisarnjaroen, Yun Ji, Nina Le Bert, Dong Li, Yao Zhang, Robert Hamatake, Nicole Tan, Chunming Li, Simone I. Strasser, Huiguo Ding, Jung-Hwan Yoon, Nigel H. Stace, Tanvir Ahmed, Dave E. Anderson, Li Yan, Antonio Bertoletti, Qing Zhu, Man-Fung Yuen
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	CHB BRII-179 immunotherapy IFN-alpha HBV-specific immune response Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/f39d5e3a799b485ca22dc42380e0af66
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spelling	oai:doaj.org-article:f39d5e3a799b485ca22dc42380e0af662021-11-20T05:11:45ZTherapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study2589-555910.1016/j.jhepr.2021.100361https://doaj.org/article/f39d5e3a799b485ca22dc42380e0af662021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589555921001373https://doaj.org/toc/2589-5559Background & 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 majority of treated patients. Overall, no notable reduction of HBsAg was observed after BRII-179 treatment. Conclusion: 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. Clinical Trial Number: ACTRN12619001210167 Lay summary: 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.Haiyan MaTien Huey LimApinya LeerapunMartin WeltmanJidong JiaYoung-suk LimPisit TangkijvanichWattana SukeepaisarnjaroenYun JiNina Le BertDong LiYao ZhangRobert HamatakeNicole TanChunming LiSimone I. StrasserHuiguo DingJung-Hwan YoonNigel H. StaceTanvir AhmedDave E. AndersonLi YanAntonio BertolettiQing ZhuMan-Fung YuenElsevierarticleCHBBRII-179immunotherapyIFN-alphaHBV-specific immune responseDiseases of the digestive system. GastroenterologyRC799-869ENJHEP Reports, Vol 3, Iss 6, Pp 100361- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CHB BRII-179 immunotherapy IFN-alpha HBV-specific immune response Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	CHB BRII-179 immunotherapy IFN-alpha HBV-specific immune response Diseases of the digestive system. Gastroenterology RC799-869 Haiyan Ma Tien Huey Lim Apinya Leerapun Martin Weltman Jidong Jia Young-suk Lim Pisit Tangkijvanich Wattana Sukeepaisarnjaroen Yun Ji Nina Le Bert Dong Li Yao Zhang Robert Hamatake Nicole Tan Chunming Li Simone I. Strasser Huiguo Ding Jung-Hwan Yoon Nigel H. Stace Tanvir Ahmed Dave E. Anderson Li Yan Antonio Bertoletti Qing Zhu Man-Fung Yuen Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study
description	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 majority of treated patients. Overall, no notable reduction of HBsAg was observed after BRII-179 treatment. Conclusion: 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. Clinical Trial Number: ACTRN12619001210167 Lay summary: 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.
format	article
author	Haiyan Ma Tien Huey Lim Apinya Leerapun Martin Weltman Jidong Jia Young-suk Lim Pisit Tangkijvanich Wattana Sukeepaisarnjaroen Yun Ji Nina Le Bert Dong Li Yao Zhang Robert Hamatake Nicole Tan Chunming Li Simone I. Strasser Huiguo Ding Jung-Hwan Yoon Nigel H. Stace Tanvir Ahmed Dave E. Anderson Li Yan Antonio Bertoletti Qing Zhu Man-Fung Yuen
author_facet	Haiyan Ma Tien Huey Lim Apinya Leerapun Martin Weltman Jidong Jia Young-suk Lim Pisit Tangkijvanich Wattana Sukeepaisarnjaroen Yun Ji Nina Le Bert Dong Li Yao Zhang Robert Hamatake Nicole Tan Chunming Li Simone I. Strasser Huiguo Ding Jung-Hwan Yoon Nigel H. Stace Tanvir Ahmed Dave E. Anderson Li Yan Antonio Bertoletti Qing Zhu Man-Fung Yuen
author_sort	Haiyan Ma
title	Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study
title_short	Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study
title_full	Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study
title_fullStr	Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study
title_full_unstemmed	Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study
title_sort	therapeutic vaccine brii-179 restores hbv-specific immune responses in patients with chronic hbv in a phase ib/iia study
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f39d5e3a799b485ca22dc42380e0af66
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Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib/IIa study

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