Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection

Wei, Miaoyan; Pan, Xingnan; Wei, Kaipeng; Li, Xuhong; Liu, Xiaolong; Zhang, Xiaoman; Jiang, Yaling; Zhang, Chunyu; Shen, Jian-kun

doi:10.1016/j.intimp.2015.06.019

Cited by 14 publications

(10 citation statements)

References 20 publications

(23 reference statements)

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“…The current prophylactic HBV vaccines, which are based on recombinant hepatitis B surface antigen (HBsAg), have successfully decreased rates of HBV infection and transmission. However, there are more than 2 billion people who have been infected with HBV and are therefore at high risk for liver failure, cirrhosis, or cancer [1]. Specific groups of patients respond poorly or not at all to conventional HBV vaccines.…”

Section: Introductionmentioning

confidence: 99%

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Wang

Liu

et al. 2017

PLoS ONE

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Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine. The results indicate that SBP could enhance the HBsAg-specific immune response, thus increasing the protection provided by the hepatitis B vaccine. The safety data obtained here warrant further investigation of SBP as a vaccine adjuvant.

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Section: Introductionmentioning

confidence: 99%

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

Wang

Liu

et al. 2017

PLoS ONE

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“…In addition, our results demonstrated that other clinical parameters such as HBV viral load and genotype, and the patient’s alanine aminotransferase level did not correlate with the ability of chronic HBV patients to respond to moDC stimulation. Several peptides of HBV, including envelope (Env 183-191 ), pre-S (Env 244-253 ), core (Core 18-27 ), and polymerase (Pol 575-583 ) have been used in DC vaccines in patients [ 21 , 30 ]. However, these peptide-pulsed DC immunotherapies depressed HBV replication, they had no effect on HBsAg levels.…”

Section: Discussionmentioning

confidence: 99%

A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion

Chen

Zhang

et al. 2018

Arch Virol

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Restoring antiviral immunity is a promising immunotherapeutic approach to the treatment of chronic hepatitis B virus (HBV) infection. Dendritic cells play a crucial role in triggering antiviral immunity. In this study, we identified immunodominant epitopes prevalent in CD8 + T cell responses. We characterized the hierarchy of HBV epitopes targeted by CD8 + T cells following autologous monocyte-derived dendritic cell (moDC) expansion in HBV-infected subjects with distinct disease stages: treatment-naïve (TN group, n = 168), treatment with complete virological response (TR group, n = 72), and resolved HBV infection (RS group, n = 28). T cell responses against 32 HBV epitopes were measured upon moDC expansion. Several subdominant epitopes that triggered HBV-specific CD8 + T cell responses were identified. These epitopes’ responses varied in individuals with different disease stages. Moreover, the most immunodominant and immunoprevalent epitope included the envelope residues 256-270 (Env 256-270 ), corresponding to amino acid residues 93-107 in the small HBV surface protein (SHBs) across three patient groups. The frequency of Env 256-270 -specific interferon-γ-producing T cells was the highest in the RS group and the lowest in the TN group. In addition, individuals with HLA-A*02:03/02:06/02:07 were capable of responding to Env 256-270 . Env 256-270 -specific CD8 + T cells tolerated amino acid variations within the epitope detected in HBV genotypes B and C. This suggests that Env 256-270 in SHBs is crucial in HBV-specific T cell immunity following autologous moDC expansion. It might be a potential target epitope for dendritic-cell-based immunotherapy for CHB patients with complete viral suppression by long-term NAs treatment. Electronic supplementary material The online version of this article (10.1007/s00705-018-4095-0) contains supplementary material, which is available to authorized users.

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“…Peptide‐pulsed autologous DCs yielded a promising tendency towards increased HBeAg seroconversion especially when added to NA therapy. Unfortunately, no T‐cell responses were assessed 61 . Responses against DNA vaccine HB‐100 (together with NA therapy) were mostly CD4 + and highest in patients with decreasing viral load.…”

Section: Past Clinical Studies On Hbv Therapeutic Vaccinationmentioning

confidence: 99%

Designing the next‐generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures

et al. 2021

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In the mid-90s, hepatitis B virus (HBV)-directed immune responses were for the first time investigated in detail and revealed suboptimal T-cell responses in chronic HBV patients. Based on these studies, therapeutic vaccination exploiting the antigen presentation capacity of dendritic cells to prime and/or boost HBVspecific T-cell responses was considered highly promising. Now, 25 years later, it has not yet delivered this promise. In this review, we summarise what has been clinically tested in terms of antigen targets and vaccine forms, how the immunological and therapeutic effects of these vaccines were assessed and what major clinical and immunological findings were reported. We combine the lessons learned from these trials with the most recent insights on HBV antigen presentation, T-cell responses, vaccine composition, antiviral and immune-modulatory drugs and disease biomarkers to derive novel opportunities for the next generation of therapeutic vaccines designed to cure chronic HBV either alone or in combination therapy.

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Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection

Cited by 14 publications

References 20 publications

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion

Designing the next‐generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures

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