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Design of therapeutic vaccines: hepatitis B as an example.

Kutscher S, Bauer T, Dembek C, Sprinzl M, Protzer U - Microb Biotechnol (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.

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Related in: MedlinePlus

General approaches for therapeutic vaccination against HBV. Protein‐ or peptide‐based vaccine strategies include immunization with immune dominant HLA‐A2‐restricted peptide epitope HBcAg18–27 and administration of HBsAg alone or in combination with the highly immunogenic HBcAg. Genetic vaccination can be performed with recombinant, replication incompetent viral vector vaccines, like MVA or adenoviruses encoding HBV DNA, or with genetically engineered HBV–DNA. Cell‐based vaccine strategies include the transfer of peptide‐loaded antigen‐presenting, autologous DC and the transfer of functional, ex vivo expanded HBV‐specific CD8+ CTL or CTL carrying HBV‐specific T‐cell receptors or chimeric antigen receptors. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBcAg, hepatitis B core antigen; anti‐HBs, antibodies against HBsAg; TCR, T‐cell receptor; CAR, chimeric antigen receptor.
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f1: General approaches for therapeutic vaccination against HBV. Protein‐ or peptide‐based vaccine strategies include immunization with immune dominant HLA‐A2‐restricted peptide epitope HBcAg18–27 and administration of HBsAg alone or in combination with the highly immunogenic HBcAg. Genetic vaccination can be performed with recombinant, replication incompetent viral vector vaccines, like MVA or adenoviruses encoding HBV DNA, or with genetically engineered HBV–DNA. Cell‐based vaccine strategies include the transfer of peptide‐loaded antigen‐presenting, autologous DC and the transfer of functional, ex vivo expanded HBV‐specific CD8+ CTL or CTL carrying HBV‐specific T‐cell receptors or chimeric antigen receptors. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBcAg, hepatitis B core antigen; anti‐HBs, antibodies against HBsAg; TCR, T‐cell receptor; CAR, chimeric antigen receptor.

Mentions: During past years a series of different therapeutic vaccination strategies (protein‐based vaccines, DNA/peptide vaccines, cell‐based vaccines) have been investigated using different animal models (i.e. HBV‐transgenic mice, woodchuck hepatitis virus model or chronically HBV‐infected chimpanzees) (Kosinska et al., 2010). Several of those strategies have reached clinical development stages with different outcomes (reviewed in Beckebaum et al., 2002; Akbar and Onji, 2005; Michel et al., 2011). Ideally, one would create vaccines that have all the properties of natural pathogens with the exception of causing disease. Key features of pathogens that can be mimicked by vaccine delivery systems are their size, shape and surface molecule organization. In addition, pathogen‐associated molecular patterns can be added to induce innate immune responses that promote adaptive immunity (Bachmann and Jennings, 2010). Figure 1 summarizes most important approaches used for therapeutic vaccination of chronic hepatitis.


Design of therapeutic vaccines: hepatitis B as an example.

Kutscher S, Bauer T, Dembek C, Sprinzl M, Protzer U - Microb Biotechnol (2011)

General approaches for therapeutic vaccination against HBV. Protein‐ or peptide‐based vaccine strategies include immunization with immune dominant HLA‐A2‐restricted peptide epitope HBcAg18–27 and administration of HBsAg alone or in combination with the highly immunogenic HBcAg. Genetic vaccination can be performed with recombinant, replication incompetent viral vector vaccines, like MVA or adenoviruses encoding HBV DNA, or with genetically engineered HBV–DNA. Cell‐based vaccine strategies include the transfer of peptide‐loaded antigen‐presenting, autologous DC and the transfer of functional, ex vivo expanded HBV‐specific CD8+ CTL or CTL carrying HBV‐specific T‐cell receptors or chimeric antigen receptors. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBcAg, hepatitis B core antigen; anti‐HBs, antibodies against HBsAg; TCR, T‐cell receptor; CAR, chimeric antigen receptor.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3815787&req=5

f1: General approaches for therapeutic vaccination against HBV. Protein‐ or peptide‐based vaccine strategies include immunization with immune dominant HLA‐A2‐restricted peptide epitope HBcAg18–27 and administration of HBsAg alone or in combination with the highly immunogenic HBcAg. Genetic vaccination can be performed with recombinant, replication incompetent viral vector vaccines, like MVA or adenoviruses encoding HBV DNA, or with genetically engineered HBV–DNA. Cell‐based vaccine strategies include the transfer of peptide‐loaded antigen‐presenting, autologous DC and the transfer of functional, ex vivo expanded HBV‐specific CD8+ CTL or CTL carrying HBV‐specific T‐cell receptors or chimeric antigen receptors. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; HBcAg, hepatitis B core antigen; anti‐HBs, antibodies against HBsAg; TCR, T‐cell receptor; CAR, chimeric antigen receptor.
Mentions: During past years a series of different therapeutic vaccination strategies (protein‐based vaccines, DNA/peptide vaccines, cell‐based vaccines) have been investigated using different animal models (i.e. HBV‐transgenic mice, woodchuck hepatitis virus model or chronically HBV‐infected chimpanzees) (Kosinska et al., 2010). Several of those strategies have reached clinical development stages with different outcomes (reviewed in Beckebaum et al., 2002; Akbar and Onji, 2005; Michel et al., 2011). Ideally, one would create vaccines that have all the properties of natural pathogens with the exception of causing disease. Key features of pathogens that can be mimicked by vaccine delivery systems are their size, shape and surface molecule organization. In addition, pathogen‐associated molecular patterns can be added to induce innate immune responses that promote adaptive immunity (Bachmann and Jennings, 2010). Figure 1 summarizes most important approaches used for therapeutic vaccination of chronic hepatitis.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstr. 30, 81675 München, Germany.

Show MeSH
Related in: MedlinePlus