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Therapeutic vaccines in treating chronic hepatitis B: the end of the beginning or the beginning of the end?

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Abstract

The antiviral treatment of chronic hepatitis B virus (HBV) infection has greatly improved over the last 20 years since it has allowed a disappearance of cirrhosis decompensation and a significant reduction of the incidence of hepatocellular carcinoma. However, a complete HBV cure has not been achieved, and alternative treatments are still needed to optimize the current treatments. Therapeutic vaccination is a promising new strategy for controlling persistent infections and tumors. However, this approach has not been as successful as initially anticipated for chronic hepatitis B. General impairment of the immune responses generated during persistent HBV infection, with exhausted T cells not responding correctly to therapeutic vaccination, is most likely responsible for the poor clinical responses observed to date. We describe here the past approaches of therapeutic vaccination, in the hope that useful lessons will emerge from these previous clinical trials. Intensive research efforts are now focusing on a better understanding of immune responses in liver, on mechanisms by which HBV escapes innate immunity and on an accurate selection of the patients susceptible to benefit of immune therapy, which could increase the efficacy of therapeutic vaccination.

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Acknowledgments

The authors thank all the physicians for their active participation in screening, including, treating and monitoring the patients, the patients for their willingness to participate to the trials, the National Agency for research on Aids and viral Hepatitis (ANRS) and the French National Institute of Health and Medical Research (Inserm) for their constant support.

Conflict of interest

M-LM received consulting fees from Transgene, ITS and Wittycell. MB has nothing to declare. HF: oral communications for Bristol-Myers Squibb, Gilead, Roche, Schering-Plough/Merck, Janssen and participation for medical congress as auditor. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec, Vertex, Gilead, Roche, Schering-Plough/Merck; Novartis, Abott, Sanofi and Glaxo Smith Kline, and grants from Bristol-Myers Squibb, Gilead, Roche and Merck/Schering-Plough.

Ethical standard

For all clinical trials for which we are co-authors, informed consent was obtained from each patient and study protocols, conformed to the ethical guidelines of the Declaration of Helsinki, were approved by the human subjects committees.

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Authors and Affiliations

  1. Laboratoire de Pathogenèse des virus de l’hépatite B, Institut Pasteur, Paris, France

    Marie-Louise Michel & Maryline Bourgine

  2. INSERM U994, Département de Virologie, Institut Pasteur, 28, rue du Docteur Roux, 75015, Paris Cedex 15, France

    Marie-Louise Michel

  3. Université Paris Descartes, Paris, France

    Hélène Fontaine & Stanislas Pol

  4. Département d’Hépatologie, Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Paris, France

    Hélène Fontaine & Stanislas Pol

  5. INSERM USM20, Institut Pasteur, Paris, France

    Stanislas Pol

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  1. Marie-Louise Michel
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  2. Maryline Bourgine
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  3. Hélène Fontaine
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  4. Stanislas Pol
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Correspondence to Marie-Louise Michel.

Additional information

This article is part of the special issue “Therapeutic vaccination in chronic hepatitis B—approaches, problems and new perspectives.”

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Michel, ML., Bourgine, M., Fontaine, H. et al. Therapeutic vaccines in treating chronic hepatitis B: the end of the beginning or the beginning of the end?. Med Microbiol Immunol 204, 121–129 (2015). https://doi.org/10.1007/s00430-014-0381-y

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