AI Article Synopsis

  • Researchers explored how combining DNA vaccination with a potent HBV neutralizing antibody might improve treatment for chronic HBV infections, which are hard to manage due to weak immune responses.
  • In a study with mice, treatment with the antibody and a DNA vaccine led to the development of specific immune cells in the liver, enhancing immune recruitment but also indicating T cells became dysfunctional over time.
  • While this combination therapy did not fully cure the infection, it showed promise by improving the immune response and providing insights into how the liver tolerates HBV.

Article Abstract

Background Aims: Successful treatment of chronic HBV infection remains a great challenge due to the difficulty in inducing efficient immune responses. Here, we investigated the therapeutic potential of DNA vaccination combined with a potent HBV broadly neutralizing antibody (bNAb) targeting the small surface viral antigen.

Approach Results: C57BL/6 mice were transduced with adeno-associated virus (AAV)-HBV and were treated twice a week with HBV bNAb for 5 weeks. A DNA-based vaccine encoding the HBV core, envelope, and polymerase proteins was administered once to mice 3 weeks after initiating of antibody therapy. The antiviral effects and antigen-specific immune responses were evaluated before and for 8 weeks after therapeutic vaccination. Vaccine administration with or without antibody treatment induced the development of functional HBV-specific CD8+ T cells and envelope-specific resident memory T cells in the liver. The combination of antibody treatment and DNA vaccination enhanced the recruitment of B and CD8+ T lymphocytes into the liver of HBV-carrier mice two weeks after vaccination. However, although still detectable 2 months after vaccination, HBV-specific CD8+ T cells showed an exhausted phenotype, suggesting that they are dysfunctional. In contrast, a more effective control of antigenemia was observed following combination therapy, which was associated with the presence of HBs-specific memory B cells.

Conclusions: Although the combination therapy did not result in a functional cure, our findings indicate it produced additive effects on the development of HBV-specific T cells in the liver immediately following treatment, offering a better insight into the mechanisms underlying hepatic tolerance.

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Source
http://dx.doi.org/10.1097/HEP.0000000000001179DOI Listing

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