Recognition of core-derived epitopes from a novel HBV-targeted immunotherapeutic by T-cells from patients infected by different viral genotypes

Vaccine. 2015 Aug 26;33(36):4548-53. doi: 10.1016/j.vaccine.2015.07.020. Epub 2015 Jul 23.


Hepatitis B virus (HBV) infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular carcinoma. Current therapies based on nucleos(t)ide analogs or pegylated-interferon-α lead to control of viral replication in most patients but rarely achieve cure. A potential strategy to control chronic hepatitis B is to restore or induce functional anti-HBV T-cell immune responses using HBV-specific immunotherapeutics. However, viral diversity is a challenge to the development of this class of products as HBV genotypes display a sequence diversity of up to 8%. We have developed a novel HBV-targeted immunotherapeutic, TG1050, based on a non-replicative Adenovirus vector encoding a unique and large fusion protein composed of multiple antigenic regions derived from a HBV genotype D sequence. Using peripheral blood mononuclear cells from 23 patients chronically infected by five distinct genotypes (gt A, B, C, D and E) and various sets of peptides encompassing conserved versus divergent regions of HBV core we have measured ability of TG1050 genotype D core-derived peptides to be recognized by T-cells from patients infected by various genotypes. Overall, PBMCs from 78% of genotype B or C- and 100% genotype A or E-infected patients lead to detection of HBV core-specific T-cells recognizing genotype D antigenic domains located both in conserved and variable regions. This proof-of-concept study supports the clinical development of TG1050 in large patient populations independently of infecting genotypes.

Keywords: Core protein; Genotypes; HBV; Immunotherapy; T-cell responses; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Cross Reactions
  • Drug Carriers
  • Epitopes / genetics
  • Epitopes / immunology*
  • Genotype
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Vaccines / genetics
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / therapy*
  • Humans
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • T-Lymphocytes / immunology*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology


  • Drug Carriers
  • Epitopes
  • Hepatitis B Core Antigens
  • Hepatitis B Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic