Lentivector expressing HBsAg and immunoglobulin Fc fusion antigen induces potent immune responses and results in seroconversion in HBsAg transgenic mice

Vaccine. 2011 May 17;29(22):3909-16. doi: 10.1016/j.vaccine.2011.03.025. Epub 2011 Mar 21.

Abstract

Even though hepatitis B virus(HBV) vaccines effectively prevent new cases of HBV infection, with approximately 350 million patients worldwide, chronic HBV infection remains a major health problem because of the associated complications (such as liver cirrhosis and hepatocellular carcinoma) and the limited treatment options. Immunotherapy has the potential to effectively control HBV replication. In this current study, we found that recombinant lentivectors could induce potent HBV surface antigen (HBsAg) specific T cell responses and humoral immune responses. Tagging the HBsAg with immunoglobulin Fc fragment further substantially increased the HBsAg specific immune responses. Remarkably, the HBS-Fc-lv lentivector could effectively break immune tolerance and induce potent HBsAg specific adaptive immune responses in HBsAg transgenic (Tg) mice with low serum level of HBsAg. More importantly, the induction of HBsAg specific immune responses in Tg mice accompanied seroconversion from HBsAg to anti-HBsAg antibody (anti-HBsAb). Our study demonstrated the potential of utilizing lentivector to treat chronic HBV infection following reduction of viral load with antiviral drug therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Vectors
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / genetics
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B, Chronic / prevention & control
  • Hepatitis B, Chronic / therapy*
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology*
  • Immunotherapy / methods*
  • Lentivirus / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic