Abstract
Hepatitis delta virus (HDV) infection may occur as coinfection with hepatitis B virus (HBV) or as superinfection of a chronically HBV-infected patient. A strong antibody response is mounted, which persists for many years; however, it is not able to modulate the course of infection. In most cases the superinfection takes a chronic course. In patients with inactive disease (HDV PCR negative) an oligospecific T-helper cell immune response and a cytotoxic T-cell response were found, which were absent in patients with persistent viremia. The role of the cellular immune response in liver injury during acute infection has not been investigated. Vaccination strategies tested in the woodchuck model induced specific B- and T-cell responses but failed to protect from HDV infection.
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References
Accapezzato D, Nisini R, Paroli M, Bruno G, Bonino F, Houghton M, Barnaba V (1998) Generation of an MHC class II-restricted T cell epitope by extracellular processing of hepatitis delta antigen. J Immunology 160:5262–5266
Allen TM, Vogel TU, Fuller DH, Mothe BR, Steffen S, Boyson JE, Shipley T, Fuller J, Hanke T, Sette A and others (2000) Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. J Immunol 164:4968–4978
Aragona M, Macagno S, Caredda F, Crivelli O, Lavarini C, Maran E, Farci P, Purcell R, Rizzetto M (1987) Serological response to the hepatitis delta virus in hepatitis D. Lancet 1:478–480
Bergmann KF, Casey JL, Tennant BC, Gerin JL (1993) Modulation of hepatitis delta virus infection by vaccination with synthetic peptides: a preliminary study in the woodchuck model. 382:181–187
Bergmann KF, Cote PJ, Moriaty A, Gerin JL (1989) Hepatitis delta antigen: antigenic structure and humoral immune response. J Immunol 143:3714–3721
Bichko V, Lemon S, Wang J, Hwang S, Lai M, Taylor J (1996) Epitopes exposed on hepatitis delta virus ribonucleoproteins. J Virol 70:5807–5811
Borghesio E, Rosina F, Smedile A, Lagget M, Niro M, Marinucci G, Rizzetto M (1998) Serum immunoglobulin M antibody to hepatitis D as a surrogate marker of hepatitis D in interferon-treated patients and in patients who underwent liver transplantation. Hepatology 27:873–876
Cavanaugh VJ, Guidotti LG, Chisari FV(1998) Inhibition of hepatitis B virus replication during adenovirus and cytomegalovirus infections in transgenic mice. J Virol 72:2630–2637
Chao Y, Lee C, Tang H, Govindarajan S, Lai M(1991)Molecular cloning and characterization of an isolate of hepatitis delta virus from Taiwan. Hepatology 13:345–352
Chisari FV, Ferrari C (1995) Hepatitis B virus immunopathogenesis. Annu Rev Immunol 13:29–60
Chu RS, Targoni OS, Krieg AM(1997) CpG oligonucleotides act as adjuvant that switch on T helper 1 (Th1) immunity. J Exp Med 10:1623–1631
D’Ugo E, Paroli M, Palmieri G, Giuseppetti R, Argentini C, Tritarelli E, Bruni R, Barnaba V, Houghton M, Rapicetta M (2004) Immunization of woodchucks with adjuvanted sHDAg (p24): immune response and outcome following challenge. Vaccine 22:457–466
Dietzschold B, Wang HH, Rupprecht CE, Celis E, Tollis M, Ertl H, Heber-Katz E, Koprowski H (1987) Induction of protective immunity against rabies by immunization with rabies virus ribonucleoprotein. Proc Natl Acad Sci USA 84:9165–9169
Dorrell L, O’Callaghan CA, Britton W, Hamleton S, McMichael A, Smith GL, Rowland-Jones S, Blanchard TJ (2000) Recombinant modified vaccinia virus Ankara efficiently restimulates human cytotoxic T lymphocytes in vitro. Vaccine 19:327–336
Eckart MR, Dong C, Houghton M, D’Urso N, Ponzetto A (1993) The effects of using recombinant vaccinia viruses expressing either large or small HDAg to protect woodchuck hepadnavirus carriers from HDV superinfection. Prog Clin Biol Res 382:201–205
Farci P, Gerin J, Aragona M, Lindsey I, Crivelli O, Balestrieri A, Smedile A, Thomas H, Rizzetto M (1986) Diagnostic and prognostic significance of the IgM antibody to the hepatitis delta virus. JAMA 255:1443–1446
Fattovich G, Boscaro S, Noventa F, Pornaro E, Stenico D, Alberti A, A. Ruol, Realdi G (1987) Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B. J Infect Dis 155:931–935
Fiedler M, Lu M, Siegel F, Whipple J, Roggendorf M (2001) Immunization of woodchucks (Marmota monax) with hepatitis delta virus DNA vaccine. Vaccine 19:4618–4626
Forsthuber T, Yip HC, Lehmann PV (1996) Induction of Th1 and Th2 immunity in neonatal mice. Science 27:1728–1730
Fu TM, Guan L, Friedman A, Schofield TL, Ulmer JB, Liu MA, Donnelly JJ (1999) Dose dependence of CTL precursor frequency by a DNA vaccine and correlation with protective immunity against influenza virus challenge. J Immunol 162:4163–4170
Govindarajan S, Gupta S, Valinluck B, Redeker A (1989) Correlation of IgM antihepatitis D virus (HDV) to HDV RNA in sera of chronic HDV. Hepatology 10:34–35
Guidotti LG, Borrow P, Hobbs MV, Matzke B, Gresser I, Oldstone MB, Chisari FV (1996a) Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver. Proc Natl Acad Sci USA 14:4589–4594
Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV (1996b) Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4:25–36
Guilhot S, Huang SN, Xia YP, Monica NL, Lai MM, Chisari FV (1994) Expression of the hepatitis delta virus large and small antigens in transgenic mice. J Virol 68:1052–1058
Huang Y, Wu J, Hsu S, Syu W (2003) Varied immunity generated in mice by DNA vaccines with large and small hepatitis delta antigens. J Virol 77:12980–12985
Huang Y-H, Tao M-H, Hu C, Syu W-J, Wu J-C (2004) Identification of novel HLAA*0201-restricted CD8+ T-cell epitopes on hepatitis delta virus. J Gen Virol 85:3089–3098
Huang Y-H, Wu J-C, Tao M-H, Syu W-J, Hsu S-H, Chi W-K, Chang F-Y, Lee S-D (2000) DNA-based immunization produces TH1 immune responses to hepatitis delta virus in a mouse model. Hepatology 32:104–110
Karayiannis P, Saldanha J, Jackson AM, Luther S, Goldin R, Monjardino J, Thomas HC (1993a) Partial control of hepatitis delta virus superinfection by immunisation of woodchucks (Marmota monax) with hepatitis delta antigen expressed by a recombinant vaccinia or baculovirus. J Med Virol 41:210–214
Karayiannis P, Saldanha J, Monjardino J, Goldin R, Main J, Luther S, Easton M, Ponzetto A, Thomas HC (1990) Immunisation of woodchucks with recombinant hepatitis delta antigen does not protect against hepatitis delta virus infection. Hepatology 12:1125–1128
Karayiannis P, Saldanha J, Monjardino J, Jackson A, Luther S, Thomas HC (1993b) Immunisation of woodchucks with hepatitis delta antigen expressed by recombinant vaccinia and baculovirus controls HDV superinfection 382:193–199
Lohrengel B, Lu M, Bauer D, Roggendorf M (2000) Expression and purification of woodchuck tumour necrosis factor alpha. Cytokine 12:573–577
Lohrengel B, Lu M, Roggendorf M (1998) Molecular cloning of the woodchuck cytokines: TNF-α, IFN-γ, and IL-6. Immunogenetics 47:332–335
Lu M, Hilken G, Kruppenbacher J, Kemper T, Schirmbeck R, Reimann J, Roggendorf M (1999) Immunization of woodchucks with plasmids expressing woodchuck hepatitis virus (WHV) core antigen and surface antigen supresses WHV infection. J Virol 73:281–289
Mauch C, Grimm C, Meckel S, Wands J, Blum H, Roggendorf M, Geissler M (2002) Induction of cytotoxic T lymphocyte responses against hepatitis delta virus antigens which protect against tumor formation in mice. Vaccine 20:170–180
Menne S, Maschke J, Tolle TK, Lu M, Roggendorf M (1997) Characterization of the T-cell response to wood chuck hepatitis virus core protein and protection of wood chucks from infection by immunization with peptides containing a T-cell epitope. J Virol 71:65–74
Murray K, Bruce SA, Hinnen A, Wingfield P, van Eerd PM, de Reus A, Schellekes H (1984) Hepatitis B virus antigens made in microbial cells immunise against viral infection. EMBO J 3:645–650
Negro F, Shapiro M, Satterfield WC, Gerin JL, Purcell RH (1989) Reappearance of hepatitis D virus (HDV) replication in chronic hepatitis B virus carrier chimpanzees rechallenged with HDV. J Infect Dis 160:567–571
Nisimi R, Paroli M, Accapezzato D, Borino F, Rosina F, Santantonio T, Sallusto F, Amoroso A, Houghton M, Barnebo V (1997) Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles. J Virol 71:2241–2251
Poisson F, Baillou A, Dubois F, Janvier B, Roingeard P, Goudeau A (1993) Immune response to synthetic peptides of hepatitis delta antigen. J Clin Microbiol 31:2343–2349
Polo J, Lim B, Govindarajan S, Lai M (1995) Replication of hepatitis delta virus RNA in mice after intramuscular injection of plasmid DNA. J Virol 69:5203–5207
Ponzetto A, Eckart M, D’Urso N, Negro F, Silvestro M, Bonino F, Wang K-S, Chien D, Choo Q-L, Houghton M (1993) Towards a vaccine for the prevention of hepatitis delta virus superinfection in HBV carriers. Prog Clin Biol Res 382:207–210
Ponzetto P, Cote PJ, Popper H, Hoyer BH, London WT, Ford EC, Bonino F, Purcell RH, Gerin JL (1984) Transmission of the hepatitis B virus associated delta agent to the eastern woodchuck. Proc Natl Acad Sci USA 81:2208–2212
Rasshofer R, Choi SS, Wölfl P, Manneck K, Weisensee U, Roggendorf M (1990) Inhibition of HDV RNA replication in vitro by Ribavirin and Suramin. In: Hollinger FB, Lemon SM, Margolis H (eds.) Viral hepatitis and liver disease. Boltimore, Williams & Wilkins, pp 659–662
Raz E, Carson DA, Parker SE, Parr TB, Abai AM, Aichinger G, Gromkowski SH, Singh M, Lew D, Yankauckas MA and others (1994) Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc Natl Acad Sci USA 91:9519–9523
Rizetto M (1981) Biology and characterization of the delta agent. In: Maynard JE, editor. Viral hepatitis. New York: The Franklin Institute Press pp 355–360
Rizetto M, Hoyer BH, Purcell RH, Gerin JL (1984) Hepatitis delta virus infection. In: Hoofnagle JH, editor. Viral Hepatitis and Liver Disease. Orlando: Grune & Stratton Inc., pp 371–379
Schirmbeck R, Melber K, Reimann J (1999) Adjuvants that enhance priming of cytotoxic T cells to a Kb-restricted epitope processed from exogenous but not endogenous hepatitis B surface antigen. Int Immunol 11:1093–1102
Schlipköter U, Ponzetto A, Fuchs K, Rasshofer R, Choi SS, Roos S, Rapicetta M, Roggendorf M(1990) Different outcome of chronic hepatitis delta virus infection in woodchucks. Liver 20:291–301
Schödel F, Neckermann G, Peterson D, Fuchs K, Fuller S, Will H, Roggendorf M(1993) Immunization with recombinant woodchuck hepatitis virus nucleocapsid antigen or hepatitis B virus nucleocapsid antigen protects hepatitis virus infection. Vaccine 11:624–628
Seizer P, Riedl P, Reimann J, Schirmbeck R (2005) Different sources of “help” facilitate the antibody response to hepatitis D virus d antigen. J Mol Med 83:225–234
Shimizu Y, Guidotti LG, Fowler P, Chisari FV (1998) Dendritic cell immunization breaks cytotoxic T lymphocyte tolerance in hepatitis B virus transgenic mice. J Immunol 161:4520–4529
Siegel F, Lu M, Roggendorf M (2001) A single immunization of woodchucks with plasmids expressing woodchuck hepatitis virus (WHV) core antigen and IFN-γ suppresses WHV infection. J Virol 75:5036–5042
Verschoor E, Mooij P, Oostermeijer H, Kolk Mvd, Haaft Pt, Verstrepen B, Sun Y, Morein B, Akerblom L, Fuller D and others (1999) Comparison of immunity generated by nucleic acid-, MF59-, and ISCOM-formulated human immunodeficiency virus type 1 vaccines in Rhesus macaques: evidence for viral clearance. J Virol 73:3292–3300
Wang D, Pearlberg J, Liu Y-T, Ganem D (2001) Deleterious effects of hepatitis delta virus replication on host cell proliferation. J Virol 75:3600–3604
Wang JG, Jansen RW, Brown EA, Lemon SM (1990) Immunogenic domains of hepatitis delta virus antigen: peptide mapping of epitopes recognised by human and woodchuck antibodies. J Virol 64:1108–1116
Webster G, Reignat S, Brown D, Ogg G, Jones L, Seneviratne S, Williams R, Dusheiko G, Bertoletti A (2004) Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. J Virol 78:5707–5719
Wu J, Chen T, Huang Y, Yen F, Ting L, Sheng W, Tsay S, Lee S (1995) Natural history of hepatitis D viral superinfection: significance of viremia detected by polymerase chain reaction. Gastroenterology 108:796–802
Yasutomi Y, Robinson HL, Lu S, Mustafa F, Lekutis C, Arthos J, Mullins JI, Voss G, Manson K, Wyand M and others (1994) Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through DNA vaccination of rhesus monkeys. J Virol 70:678–681
Yokoyama M, Zhang J, Whitton JL (1995) DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection. JVirol 69:2684–2688
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Fiedler, M., Roggendorf, M. (2006). Immunology of HDV Infection. In: Casey, J.L. (eds) Hepatitis Delta Virus. Current Topics in Microbiology and Immunology, vol 307. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-29802-9_10
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DOI: https://doi.org/10.1007/3-540-29802-9_10
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