Multiple doses of hepatitis B recombinant vaccine for chronic hepatitis B patients with low surface antigen levels: a pilot study

Lai, Ming‐Wei; Hsu, Chao‐Wei; Lin, Chih‐Lang; Chien, Rong‐Nan; Lin, Wey‐Ran; Chang, Chun‐Shin; Liang, Kung–Hao; Yeh, Chau‐Ting

doi:10.1007/s12072-018-9890-x

Cited by 16 publications

(10 citation statements)

References 29 publications

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“…More promising results were obtained by administration of recombinant vaccine in people with low HBsAg levels, which was associated with further reductions in HBsAg titres and undetectable HBsAg in some participants. However, there was no prospective control arm in this study ( 91 ). Larger randomized studies are warranted to assess whether recombinant vaccines have a role in treating individuals with low baseline HBsAg levels.…”

Section: Previous Clinical Trials Of Therapeutic Vaccination In Chronic Hbvmentioning

confidence: 95%

Therapeutic vaccination for treatment of chronic hepatitis B

Cargill

Barnes

2021

Clinical and Experimental Immunology

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Section: Previous Clinical Trials Of Therapeutic Vaccination In Chronic Hbvmentioning

confidence: 95%

Therapeutic vaccination for treatment of chronic hepatitis B

Cargill

Barnes

2021

Clinical and Experimental Immunology

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“…Thus, the rational selection of patients with low levels of serum HBsAg after long term NAs treatment could be employed to optimize the therapeutic efficacy of B cell targeting vaccination. Indeed, in a recent study, conventional HBsAg-based vaccination in 20 HBeAg-negative patients with HBsAg <1,000 IU/ml, resulted in a significant HBsAg decline in 14 patients and HBsAg loss in 2 patients (128). In another study, the switch from long-term entecavir (ETV) treatment to a combined therapy with IFN-alpha-2b, HBsAg-based vaccination, and IL-2 resulted in a higher HBsAg loss rate (9.38%) compared to IFN-alpha-2b (3.03%) alone or continued entecavir (3.70%) therapy in HBeAg-negative patients.…”

Section: How To Optimize the Therapeutic Efficacy Of Strategies Targementioning

confidence: 99%

Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response

Zhang

Shicheng

et al. 2019

Front. Immunol.

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The central role of the cellular immune response in the control and clearance of the hepatitis B virus (HBV) infection has been well-established. The contribution of humoral immunity, including B cell and antibody responses against HBV, has been investigated for a long time but has attracted increasing attention again in recent years. The anti-HBs antibody was first recognized as a marker of protective immunity after the acute resolution of the HBV infection (or vaccination) and is now defined as a biomarker for the functional cure of chronic hepatitis B (CHB). In this way, therapies targeting HBV-specific B cells and the induction of an anti-HBs antibody response are essential elements of a rational strategy to terminate chronic HBV infection. However, a high load of HBsAg in the blood, which has been proposed to induce antigen-specific immune tolerance, represents a major obstacle to curing CHB. Long-term antiviral treatment by nucleoside analogs, by targeting viral translation by siRNA, by inhibiting HBsAg release via nucleic acid polymers, or by neutralizing HBsAg via specific antibodies could potentially reduce the HBsAg load in CHB patients. A combined strategy including a reduction of the HBsAg load via the above treatments and the therapeutic targeting of B cells by vaccination may induce the appearance of anti-HBs antibodies and lead to a functional cure of CHB.

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“…Therefore, therapeutic effect of B cells targeted vaccination could be optimized through selecting reasonably upon patients with low HBsAg levels who have been treated with NAs for a long time. Actually, a recent study enrolled 20 patients with negative HBeAg as well as HBsAg < 1000 IU/ml and found that HBsAg decreased significantly in 14 patients, and 2 patients had a HBsAg loss after inoculated conventional HBsAg-based vaccination ( 96 ). Another research showed that for HBeAg-negative patients, switching from long-term ETV therapy to adding HBsAg-based vaccination, IFNα-2b and IL-2 as a combination, there was a higher rate of HBsAg loss (9.38%) compared with patients using IFNα-2b alone (3.03%) or continuing entecavir (3.70%) treatment .…”

Section: Chb Functional Cure and Host Immune Responsementioning

confidence: 99%

Hepatitis B functional cure and immune response

2022

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Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may “wake up” immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the “dominant population” for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

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Multiple doses of hepatitis B recombinant vaccine for chronic hepatitis B patients with low surface antigen levels: a pilot study

Abstract: In low-level HBsAg CHB patients, serial HBsAg-based vaccinations were safe, resulting in significant HBsAg decline. HLA gene expression and genotypes played a role in vaccine responsiveness (ClinicalTrials.gov Identifier: NCT01817725).

Cited by 16 publications

References 29 publications

Therapeutic vaccination for treatment of chronic hepatitis B

Therapeutic vaccination for treatment of chronic hepatitis B

Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response

Hepatitis B functional cure and immune response

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