A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice

Buchmann, Pascale; Dembek, Claudia J.; Kuklick, Larissa; Jäger, Clemens; Tedjokusumo, Raindy; Freyend, Miriam John von; Drebber, Uta; Janowicz, Zbigniew A.; Melber, Karl; Protzer, Ulrike

doi:10.1016/j.vaccine.2012.12.074

Cited by 83 publications

(59 citation statements)

References 37 publications

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“…Many experimental HBV vaccines, such as DNA and new-adjuvant vaccines, have been also investigated for improving therapeutic vaccines to break HBV immune tolerance (26, 27). These studies demonstrate that both antibody response and proper CTL response are required for partially breaking HBV tolerance.…”

Section: Discussionmentioning

confidence: 99%

Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination

Zhu

Liu

Yang

et al. 2016

The Journal of Immunology

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Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection (CHB) has been challenging due to HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface antigen in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg antibody in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist, resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral antigen with neutralizing antibodies followed by vaccination.

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Section: Discussionmentioning

confidence: 99%

Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination

Zhu

Liu

Yang

et al. 2016

The Journal of Immunology

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“…In most cases, antigen-presenting dendritic cells (DCs) were used as an adjuvant or vehicle to stimulate immunocytes of HBV carriers. Accumulated data have shown that DC-based therapeutic vaccines represented better therapeutic options for treating HBV-infected HBV TM compared to the effects of only antigen-based therapeutic vaccines (37,(42)(43)(44)(45)(46).…”

Section: Immune Therapy In Animal Models Of Chronic Hbv Infection Andmentioning

confidence: 99%

Immune therapy for hepatitis B

et al. 2016

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Although several antiviral drugs are now available for treatment of patients with chronic hepatitis B (CHB), sustained off-treatment clinical responses and containment of CHB-related complications are not achieved in majority of CHB patients by antiviral therapy. In addition, use of these drugs is endowed with substantial long term risk of viral resistance and drug toxicity. The infinite treatment regimens of antiviral drugs for CHB patients are also costly and usually unbearable by most patients of developing and resource-constrained countries.Taken together, there is a pressing need to develop new and innovative therapeutic approaches for CHB patients.

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“…Clinical trials using vaccines containing HBcAg and HBsAg peptides showed a reduction of HBV replication that that were not accompanied by HBsAg clearance [95,96] . However, a recent vaccine formulation that comprised HBsAg and HBcAg particles and was delivered together with a saponin based ISCOMATRIX adjuvant in transgenic mice induced the activation HBsAg-and HBcAg-specific CTLs and the high production of their antibody [97] .…”

Section: Therapeutic Vaccinationmentioning

confidence: 99%

Current and future antiviral drug therapies of hepatitis B chronic infection

Koumbi¹

2015

WJH

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Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon (IFN)-α and monotherapy with five nucleos(t)ide analogues (NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish longterm control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection. Core tip: Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem. Current therapeutic regimens include pegylated-interferon (IFN)-α and nucleos(t)ide analogues (NAs). Both treatments do not eradicate the virus and have numerous limitations. IFN therapy is of finite duration and has low response rates while longterm NA therapies have a high risk of drug resistance. The development of new therapeutic approaches is imperative. This review brings together current treatments and the ongoing research efforts on evaluating potential therapeutic strategies that target the suppression of HBV replication the restoration of the weak immune responses against HBV.

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A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice

Cited by 83 publications

References 37 publications

Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination

Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination

Immune therapy for hepatitis B

Current and future antiviral drug therapies of hepatitis B chronic infection

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