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

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

Author information

  • 1Laboratoire de Pathogenèse des virus de l'hépatite B, Département de Virologie, Institut Pasteur, 28, rue du Docteur Roux, Paris Cedex 15 75724, France.
  • 2Transgene SA, Department of Infectious Diseases, Lyon, France.
  • 3Virology Unit, Cochin Hospital, Paris, France.
  • 4Laboratoire de Pathogenèse des virus de l'hépatite B, Département de Virologie, Institut Pasteur, 28, rue du Docteur Roux, Paris Cedex 15 75724, France; INSERM U994, Département de Virologie, Institut Pasteur, Paris, France. Electronic address: marie-louise.michel@pasteur.fr.

Abstract

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

PMID:
26209840
DOI:
10.1016/j.vaccine.2015.07.020
[PubMed - indexed for MEDLINE]
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