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      Design of therapeutic vaccines: hepatitis B as an example

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          Summary

          Therapeutic vaccines are currently developed for chronic viral infections, such as human papillomavirus (HPV), human immunodeficiency virus (HIV), herpesvirus and hepatitis B (HBV) and C (HCV) virus infections. As an alternative to antiviral treatment or to support only partially effective therapy a therapeutic vaccine shall activate the patient's immune system to fight and finally control or ideally even eliminate the virus. Whereas the success of prophylactic vaccination is based on rapid neutralization of the invading pathogen by antibodies, virus control and elimination of infected cells require T cells. Therefore, induction of a multi‐specific and multifunctional T‐cell response against key viral antigens is a paradigm of therapeutic vaccination – besides activation of a humoral immune response to limit virus spread. In this review, we describe options to develop a therapeutic vaccine for chronic viral infections using HBV as a promising example.

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          Immunology of hepatitis B virus and hepatitis C virus infection.

          Barbara Rehermann, Michelina Nascimbeni (2005)
          More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and survival strategies. This review assesses recent advances in our understanding of viral hepatitis, contrasts mechanisms of virus-host interaction in acute hepatitis B and hepatitis C, and outlines areas for future studies.
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            Is Open Access

            Control of cccDNA function in hepatitis B virus infection.

            Massimo Levrero, Teresa Pollicino, Jörg Petersen … (2009)
            The template of hepatitis B virus (HBV) transcription, the covalently closed circular DNA (cccDNA), plays a key role in the life cycle of the virus and permits the persistence of infection. Novel molecular techniques have opened new possibilities to investigate the organization and the activity of the cccDNA minichromosome in vivo, and recent advances have started to shed light on the complexity of the mechanisms controlling cccDNA function. Nuclear cccDNA accumulates in hepatocyte nuclei as a stable minichromosome organized by histone and non-histone viral and cellular proteins. Identification of the molecular mechanisms regulating cccDNA stability and its transcriptional activity at the RNA, DNA and epigenetic levels in the course of chronic hepatitis B (CH-B) infection may reveal new potential therapeutic targets for anti-HBV drugs and hence assist in the design of strategies aimed at silencing and eventually depleting the cccDNA reservoir.
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              DNA vaccines: an historical perspective and view to the future.

              Aiqin Liu (2010)
              This review provides a detailed look at the attributes and immunologic mechanisms of plasmid DNA vaccines and their utility as laboratory tools as well as potential human vaccines. The immunogenicity and efficacy of DNA vaccines in a variety of preclinical models is used to illustrate how they differ from traditional vaccines in novel ways due to the in situ antigen production and the ease with which they are constructed. The ability to make new DNA vaccines without needing to handle a virulent pathogen or to adapt the pathogen for manufacturing purposes demonstrates the potential value of this vaccine technology for use against emerging and epidemic pathogens. Similarly, personalized anti-tumor DNA vaccines can also readily be made from a biopsy. Because DNA vaccines bias the T-helper (Th) cell response to a Th1 phenotype, DNA vaccines are also under development for vaccines against allergy and autoimmune diseases. The licensure of four animal health products, including two prophylactic vaccines against infectious diseases, one immunotherapy for cancer, and one gene therapy delivery of a hormone for a food animal, provides evidence of the efficacy of DNA vaccines in multiple species including horses and pigs. The size of these target animals provides evidence that the somewhat disappointing immunogenicity of DNA vaccines in a number of human clinical trials is not due simply to the larger mass of humans compared with most laboratory animals. The insights gained from the mechanisms of protection in the animal vaccines, the advances in the delivery and expression technologies for increasing the potency of DNA vaccines, and encouragingly potent human immune responses in certain clinical trials, provide insights for future efforts to develop DNA vaccines into a broadly useful vaccine and immunotherapy platform with applications for human and animal health. © 2010 John Wiley & Sons A/S.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Microb Biotechnol
                Journal ID (iso-abbrev): Microb Biotechnol
                Journal ID (publisher-id): MBT
                Title: Microbial biotechnology
                Publisher: Blackwell Publishing Ltd (Oxford, UK )
                ISSN (Print): 1751-7915
                ISSN (Electronic): 1751-7915
                Publication date (Print): March 2012
                Publication date (Electronic): 20 February 2012
                Volume: 5
                Issue: 2
                Pages: 270-282
                Affiliations
                Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.
                Author notes
                [†]

                Both authors contributed equally. Conflicts of Interest: U.P. is a consultant of Dynavax/Rheinbiotech for scientific aspects of HBV vaccine development. S.K., T.B., C.D. and M.S. declare no conflict of interest.

                *E‐mail protzer@ 123456tum.de ; protzer@ 123456helmholtz‐muenchen.de ; Tel. (+49) 89 4140 6821; Fax (+49) 89 4140 6823.
                Article
                DOI: 10.1111/j.1751-7915.2011.00303.x
                PMC ID: 3815787
                PubMed ID: 21958338
                SO-VID: 82b86d04-486b-4144-ae84-fba2b441eaee
                Copyright © Copyright © 2011 The Authors. Microbial Biotechnology © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd
                History
                Date received : 07 July 2011
                Date revision received : 22 August 2011
                Date accepted : 22 August 2011
                Categories
                Subject: Research Articles

                ScienceOpen disciplines: Biotechnology
                Data availability:
                ScienceOpen disciplines: Biotechnology

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