This study used a duck hepatitis B virus (DHBV) model to evaluate whether a novel DNA vaccination protocol alone or associated with antiviral (lamivudine) treatment was able to clear the intrahepatic covalently closed, circular viral DNA (cccDNA) pool responsible for persistence of infection. DHBV carriers received DNA vaccine (on weeks 6, 10, 13, 14, 28 and 35) targeting the large envelope and/or core proteins alone or combined with lamivudine treatment (on weeks 1-8) or lamivudine monotherapy. After 10 months of follow-up, a dramatic decrease in viraemia and liver DHBV cccDNA (below 0.08 cccDNA copies per cell) was observed in 9/30 ducks (30 %) receiving DNA mono- or combination therapy, compared with 0/12 (0 %) from lamivudine monotherapy or the control groups, suggesting a significant antiviral effect of DNA immunization. However, association with the drug did not significantly improve DHBV DNA vaccine efficacy (33 % cccDNA clearance for the combination vs 27 % for DNA monotherapy), probably due to the low antiviral potency of lamivudine in the duck model. Seroconversion to anti-preS was observed in 6/9 (67 %) ducks showing cccDNA clearance, compared with 1/28 (3.6 %) without clearance, suggesting a significant correlation (P<0.001) between humoral response restoration and cccDNA elimination. Importantly, an early (weeks 10-12) drop in viraemia was observed in seroconverted animals, and virus replication did not rebound following the cessation of immunotherapy, indicating a sustained effect. This study provides the first evidence that therapeutic DNA vaccination is able to enhance hepadnaviral cccDNA clearance, which is tightly associated with a break in humoral immune tolerance. These results also highlight the importance of antiviral drug potency and an effective DNA immunization protocol for the design of therapeutic vaccines against chronic hepatitis B.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1099/vir.0.83583-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Virological Response to Lamivudine and Tenofovir Treatment in a Mono-infected Chronic Hepatitis B Patient with Potential Tenofovir Resistance: A Case Report.
J Clin Transl Hepatol
January 2025
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Few cases of tenofovir resistance have been reported, and the appropriate treatment for such cases remains unclear. We aimed to share a case of a chronic hepatitis B mono-infected patient with potential tenofovir resistance who required combined lamivudine and tenofovir therapy to achieve adequate viral suppression. The patient's viral load (plasma) was monitored using the cobas® hepatitis B virus Test on the cobas® 6800 system.
View Article and Find Full Text PDFFunctional cure of a young child with chronic hepatitis B cirrhosis treated by pegylated interferon α combination therapy: A case report.
Medicine (Baltimore)
January 2025
Jumei Doctor Group Medical (Shenzhen) Co., Ltd, Shenzhen, China.
Rationale: Current research on antiviral treatment in children is relatively limited, especially in children under 1 year old.
Patient Concerns: Liu XX, an 8-month-old infant (case number: 3001120473), presented to the hospital in August 2016 with a chief complaint of being "hepatitis B surface antigen positive for 8 months and experiencing abnormal liver function for 5 months."
Diagnoses: The patient was diagnosed as chronic hepatitis B cirrhosis (G3S3-4) with active compensatory phase.
Safety and efficacy of lamivudine/dolutegravir vs. bictegravir/emtricitabine/tenofovir alafenamide in antiretroviral-naive adults with HIV-1 infection in Shanghai, China: a single-centre retrospective study.
J Med Microbiol
January 2025
Department of Infection and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, PR China.
Lamivudine plus dolutegravir (3TC/DTG) and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimens are commonly used as first-line treatments for people living with human immunodeficiency virus (HIV) (PLWH) worldwide. There are limited comparative data on the antiviral activity and safety between these regimens in ART-naive PLWH, particularly in China, where the 3TC/DTG regimen was integrated into first-line therapy in 2021 and gained broader adoption after its inclusion in the National Health Insurance in 2022. This study aims to provide real-world evidence comparing the 3TC/DTG regimen to the B/F/TAF regimen in ART-naive PLWH in China.
View Article and Find Full Text PDFThymidine Analogue Mutations with M184V Significantly Decrease Phenotypic Susceptibility of HIV-1 Subtype C Reverse Transcriptase to Islatravir.
Viruses
December 2024
HIV Pathogenesis Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Islatravir (ISL) is the first-in-class nucleoside reverse transcriptase translocation inhibitor (NRTtI) with novel modes of action. Data on ISL resistance are currently limited, particularly to HIV-1 non-B subtypes. This study aimed to assess prevalent nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistant mutations in HIV-1 subtype C for their phenotypic resistance to ISL.
View Article and Find Full Text PDFEffectiveness and Tolerability of DOR/3TC/TDF in Experienced People with HIV Switching from RPV/FTC/TDF: A Retrospective, Single Center Cohort Study.
Pharmaceuticals (Basel)
December 2024
Viral Immunodeficiencies Unit, Clinical Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Via Portuense 292, 00149 Roma, Italy.
With advances in antiretroviral therapy for HIV treatment, newer drug combinations provide improved efficacy, safety, and compliance. This study evaluates switching to a regimen of doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) in a cohort of people living with HIV (PLWH). this Italian retrospective study included 426 PLWH who switched from rilpivirine (RPV)/TDF/emtricitabine (FTC) to DOR/3TC/TDF.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!