Innovative Breakthrough Non-Integrating Lentiviral Vector Therapeutic Hepatitis B Vaccine Demonstrates Significant Efficacy
Time:2023-10-11
A groundbreaking paper titled "Therapeutic Vaccination with Lentiviral Vector in HBV-Persistent Mice and Two Inactive HBsAg Carriers" has recently been published in the prestigious Journal of Hepatology (Impact Factor 26). The study was conducted by a collaborative research team including Chao Qiu and Wenhong Zhang, professors at Fudan University; Hong Wu, a doctor at Changzhi People's Hospital; and Pierre Charneau, professor at Université de Paris Cité. The research successfully developed a novel non-integrating lentiviral vector therapeutic hepatitis B vaccine and validated its remarkable antiviral efficacy in both animal models and human trials.
The vaccine exhibited exceptional antigen-specific T-cell induction in a mouse model with persistent hepatitis B virus (HBV) infection, effectively reducing serum hepatitis B surface antigen (HBsAg) levels and viral loads. Over a 34-week observation period, six out of ten vaccinated mice (60%) achieved complete clearance of serum HBsAg, with a significant reduction in the number of HBV-positive hepatocytes in their livers.
Additionally, exploratory assessments of two inactive HBsAg carriers showed promising results. One patient experienced a notable increase in the number of peripheral blood-specific T-cells following vaccination, while the other exhibited a detectable but mild response, with declining HBsAg levels from baseline. This advancement represents a significant step forward in the treatment of chronic HBV infection.
Chronic hepatitis B virus (HBV) infection is a major global health challenge. While current antiviral drugs can effectively suppress HBV replication, treatment often requires prolonged periods and remains difficult to cure. This is primarily due to the host's inadequate anti-HBV immune response, a hallmark of chronic HBV immunopathogenesis.
Researchers have explored various innovative immunotherapies aimed at enhancing HBV-specific T-cells, many of which have been evaluated in clinical trials. Among these, therapeutic vaccines can directly and selectively boost residual HBV-specific T-cells. In this study, the research team designed non-integrating lentiviral vectors (LVs) expressing HBV core antigen (LV-core), preS1 antigen (LV-preS1), or large HBsAg antigen (LV-LHBs). They assessed the immunogenicity of these vectors in HBV-naive mice and evaluated their therapeutic potential in mice with persistent HBV infection. Subsequent safety assessments of LV-LHBs were conducted on the two inactive HBsAg carriers, demonstrating their ability to induce LHBs-specific T-cell responses and reduce serum HBsAg levels. Overall, this study provides compelling evidence that LV-based therapeutic vaccination can enhance HBsAg-specific immune responses in both mice with persistent HBV infection and patients with chronic HBV infection.
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