Induction or expansion of T-cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers

Authors

  • Maryline Mancini-Bourgine,

    1. Carcinogénèse Hépatique et Virologie Moléculaire/Institut National de la Santé et de la Recherche Médicale Unité 370, Institut Pasteur, Paris, France
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  • Hélène Fontaine,

    1. Service d'Hépatologie, Hôpital Necker Enfants Malades, Paris, France
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  • Daniel Scott-Algara,

    1. Unité de Biologie des Rétrovirus, Institut Pasteur, Paris, France
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  • Stanislas Pol,

    1. Service d'Hépatologie, Hôpital Necker Enfants Malades, Paris, France
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  • Christian Bréchot,

    1. Carcinogénèse Hépatique et Virologie Moléculaire/Institut National de la Santé et de la Recherche Médicale Unité 370, Institut Pasteur, Paris, France
    2. Service d'Hépatologie, Hôpital Necker Enfants Malades, Paris, France
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  • Marie-Louise Michel

    Corresponding author
    1. Carcinogénèse Hépatique et Virologie Moléculaire/Institut National de la Santé et de la Recherche Médicale Unité 370, Institut Pasteur, Paris, France
    • CHVM/INSERM U 370, Département de Médecine Moléculaire, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris, France
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    • fax: (33) 1-45-68-89-43


Abstract

Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Viral persistence is thought to be related to poor HBV-specific T-cell responses. A phase I clinical trial was performed in chronic HBV carriers to investigate whether HBV DNA vaccination could restore T-cell responsiveness. Ten patients with chronic active hepatitis B nonresponder to approved treatments for HBV infection were given 4 intramuscular injections of 1 mg of a DNA vaccine encoding HBV envelope proteins. HBV-specific T-cell responses were assessed by proliferation, ELISpot assays, and tetramer staining. Secondary end points included safety and the monitoring of HBV viraemia and serological markers. Proliferative responses to hepatitis B surface antigen were detected in two patients after DNA injections. Few HBV-specific interferon γ–secreting T cells were detectable before immunization, but the frequency of such responses was significantly increased by 3 DNA injections. Immunization was well tolerated. Serum HBV DNA levels decreased in 5 patients after 3 vaccine injections, and complete clearance was observed in 1 patient. In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective. We demonstrate that DNA vaccination can specifically but transiently activate T-cell responses in some chronic HBV carriers who do not respond to current antiviral therapies. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;40:874–882.)

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