Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?

The prolonged viral antigen stimulation is the driving force for the development of immune tolerance to chronic hepatitis B virus (HBV) infection. The sustained reduction of viral proteins may allow for the recovery and efficient activation of HBV-specific T and B cells by immune-stimulating agents,...

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Main Authors: Sisi Yang, Wanjia Zeng, Jiming Zhang, Fengmin Lu, Jinhong Chang, Ju-Tao Guo
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2021.1952851
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author Sisi Yang
Wanjia Zeng
Jiming Zhang
Fengmin Lu
Jinhong Chang
Ju-Tao Guo
author_facet Sisi Yang
Wanjia Zeng
Jiming Zhang
Fengmin Lu
Jinhong Chang
Ju-Tao Guo
author_sort Sisi Yang
collection DOAJ
description The prolonged viral antigen stimulation is the driving force for the development of immune tolerance to chronic hepatitis B virus (HBV) infection. The sustained reduction of viral proteins may allow for the recovery and efficient activation of HBV-specific T and B cells by immune-stimulating agents, checkpoint blockades and/or therapeutic vaccinations. Recently, several therapeutic approaches have been shown to significantly reduce intrahepatic viral proteins and/or circulating HBV surface antigen (HBsAg) with variable impacts on the host antiviral immune responses in animal models or human clinical trials. It remains to be further investigated whether reduction of viral protein expression or induction of intrahepatic viral protein degradation is more efficacious to break the immune tolerance to chronic HBV infection. It is also of great interest to know if the accelerated clearance of circulating HBsAg by antibodies has a long-term immunological impact on HBV infection and disease progression. Although it is clear that removal of antigen stimulation alone is not sufficient to induce the functional recovery of exhausted T and B cells, accumulating evidence suggests that the reduction of viral antigen load appears to facilitate the therapeutic activation of functional antiviral immunity in chronic HBV carriers. Based on a systematic review of the findings in animal models and clinical studies, the research directions toward discovery and development of more efficacious therapeutic approaches to reinvigorate HBV-specific adaptive immune function and achieve the durable control of chronic HBV infection, i.e. a functional cure, in the vast majority of treated patients are discussed.
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institution Kabale University
issn 2222-1751
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spelling doaj-art-c22cb7acfba643bc8b15345d3d0678742025-08-20T03:52:56ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011011545155410.1080/22221751.2021.1952851Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?Sisi Yang0Wanjia Zeng1Jiming Zhang2Fengmin Lu3Jinhong Chang4Ju-Tao Guo5Baruch S. Blumberg Institute, Doylestown, PA, USAPeking University Health Science Center, Beijing, People’s Republic of ChinaHuashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaPeking University Health Science Center, Beijing, People’s Republic of ChinaBaruch S. Blumberg Institute, Doylestown, PA, USABaruch S. Blumberg Institute, Doylestown, PA, USAThe prolonged viral antigen stimulation is the driving force for the development of immune tolerance to chronic hepatitis B virus (HBV) infection. The sustained reduction of viral proteins may allow for the recovery and efficient activation of HBV-specific T and B cells by immune-stimulating agents, checkpoint blockades and/or therapeutic vaccinations. Recently, several therapeutic approaches have been shown to significantly reduce intrahepatic viral proteins and/or circulating HBV surface antigen (HBsAg) with variable impacts on the host antiviral immune responses in animal models or human clinical trials. It remains to be further investigated whether reduction of viral protein expression or induction of intrahepatic viral protein degradation is more efficacious to break the immune tolerance to chronic HBV infection. It is also of great interest to know if the accelerated clearance of circulating HBsAg by antibodies has a long-term immunological impact on HBV infection and disease progression. Although it is clear that removal of antigen stimulation alone is not sufficient to induce the functional recovery of exhausted T and B cells, accumulating evidence suggests that the reduction of viral antigen load appears to facilitate the therapeutic activation of functional antiviral immunity in chronic HBV carriers. Based on a systematic review of the findings in animal models and clinical studies, the research directions toward discovery and development of more efficacious therapeutic approaches to reinvigorate HBV-specific adaptive immune function and achieve the durable control of chronic HBV infection, i.e. a functional cure, in the vast majority of treated patients are discussed.https://www.tandfonline.com/doi/10.1080/22221751.2021.1952851Hepatitis B virusHBsAgimmune toleranceimmunotherapytherapeutic vaccination
spellingShingle Sisi Yang
Wanjia Zeng
Jiming Zhang
Fengmin Lu
Jinhong Chang
Ju-Tao Guo
Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?
Emerging Microbes and Infections
Hepatitis B virus
HBsAg
immune tolerance
immunotherapy
therapeutic vaccination
title Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?
title_full Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?
title_fullStr Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?
title_full_unstemmed Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?
title_short Restoration of a functional antiviral immune response to chronic HBV infection by reducing viral antigen load: if not sufficient, is it necessary?
title_sort restoration of a functional antiviral immune response to chronic hbv infection by reducing viral antigen load if not sufficient is it necessary
topic Hepatitis B virus
HBsAg
immune tolerance
immunotherapy
therapeutic vaccination
url https://www.tandfonline.com/doi/10.1080/22221751.2021.1952851
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