ArticlePLoS pathogens2014
Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.
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Who cites it
126 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.
- Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.Infectious diseases of poverty · 2023Pooled it
- Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy.The Journal of infectious diseases · 2017Trial
- PD-1/PD-L1 blockade as part of combination strategies toward functional cure of chronic hepatitis B.Frontiers in immunology · 2026Review
- From exhaustion to functional cure: frontiers in reversing HBV-specific T-cell immunity.Frontiers in immunology · 2026Review
- Nanocarrier-based immunotherapy for viral diseases.International journal of pharmaceutics: X · 2025Review
- Immunological aspects of naturally occurring model of hepatitis B virus (HBV) infection, hepatitis B, and HBV-associated hepatocellular carcinoma in the American woodchuck Marmota monax.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Functional Cure for Hepatitis B Virus: Challenges and Achievements.International journal of molecular sciences · 2025Review
- Acid ceramidase regulates CD8+ T-cell exhaustion via type I interferon-mediated upregulation of PD-L1.Frontiers in immunology · 2025Article
- IL-2 and IL-15 augment HBV therapeutic vaccination and PD1 blockade for functional cure in the AAV-HBV mouse model.Frontiers in immunology · 2025Article
- PD-L1: From cancer immunotherapy to therapeutic implications in multiple disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Prophylactic and therapeutic vaccine development: advancements and challenges.Molecular biomedicine · 2024Review
- Discontinuation of Nucleos(t)ide Analogues in HBeAg Negative Chronic Hepatitis B Patients: Risks and Benefits.Infectious diseases & clinical microbiology · 2024Review
- Genetic and transcriptomic analyses of diffuse large B-cell lymphoma patients with poor outcomes within two years of diagnosis.Leukemia · 2024Article
- Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection.Digestive diseases (Basel, Switzerland) · 2024Review
- Recent advances in understanding T cell activation and exhaustion during HBV infection.Virologica Sinica · 2023Review
- New Treatment Options in Chronic Hepatitis B: How Close Are We to Cure?Infectious diseases & clinical microbiology · 2023Review
- HBV001: Phase I study evaluating the safety and immunogenicity of the therapeutic vaccine ChAdOx1-HBV.JHEP reports : innovation in hepatology · 2023Article
- Utility of novel viral and immune markers in predicting HBV treatment endpoints: A systematic review of treatment discontinuation studies.JHEP reports : innovation in hepatology · 2023Article
- Progressive Multifocal Leukoencephalopathy Treated by Immune Checkpoint Inhibitors.Annals of neurology · 2023Article
- Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation.Frontiers in immunology · 2023Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1). Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1) interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV) infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV), therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.