1887

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Volume 83, Issue 2

Hepatitis C virus non-structural protein 3-specific cellular immune responses following single or combined immunization with DNA or recombinant Semliki Forest virus particles Free

Abstract

The capacity of recombinant Semliki Forest virus particles (rSFV) expressing the hepatitis C virus non-structural protein 3 (NS3) to induce, in comparison or in combination with an NS3-expressing plasmid, specific cellular and humoral immune responses in murine models was evaluated. studies indicated that both types of vaccine expressed the expected size protein, albeit with different efficacies. The use of mice transgenic for the human HLA-A2.1 molecule indicated that the rSFV-expressed NS3 protein induces, as shown previously for an NS3 DNA vaccine, NS3-specific cytotoxic lymphocytes (CTLs) targeted at one dominant HLA-A2 epitope described in infected patients. All DNA/rSFV vaccine combinations evaluated induced specific CTLs, which were detectable for up to 31 weeks after the first injection. Overall, less than 1 log difference was observed in terms of the vigour of the bulk CTL response induced and the CTL precursor frequency between all vaccines (ranging from 1:2·6×10 to 1:1×10). Anti-NS3 antibodies could only be detected following a combined vaccine regimen in non-transgenic BALB/c mice. In conclusion, rSFV particles expressing NS3 are capable of inducing NS3-specific cellular immune responses targeted at a major HLA-A2 epitope. Such responses were comparable to those obtained with a DNA-based NS3 vaccine, whether in the context of single or combined regimens.

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© Microbiology Society
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2002-02-01
2024-04-23
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References

  1. Alter H. J., Purcell R. H., Holland P. V., Popper H. 1978; Transmissible agent in non-A, non-B hepatitis. Lancet i:459–463
     [Google Scholar]
  2. Amara R. R., Villinger F., Altman J. D., Lydy S. L., O’Neil S. P., Staprans S. I., Montefiori D. C. and others 2001; Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292:69–74
     [Google Scholar]
  3. Bain C., Fatmi A., Zoulim F., Zarski J. P., Trepo C., Inchauspé G. 2001; Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 120:512–524
     [Google Scholar]
  4. Barouch D. H., Santra S., Schmitz J. E., Kuroda M. J., Fu T.-M., Wagner W., Bilska M. and others 2000; Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290:486–492
     [Google Scholar]
  5. Battegay M., Fikes J., Di Bisceglie A. M., Wentworth P. A., Sette A., Celis E., Ching W. M., Grakoui A., Rice C. M., Kurokohchi K. and others 1995; Patients with chronic hepatitis C have circulating cytotoxic T cells which recognize hepatitis C virus-encoded peptides binding to HLA-A2.1 molecules. Journal of Virology 69:2462–2470
     [Google Scholar]
  6. Baumert T. F., Vergalla J., Satoi J., Thomson M., Lechmann M., Herion D., Greenberg H. B., Ito S., Liang T. J. 1999; Hepatitis C virus-like particles synthesized in insect cells as a potential vaccine candidate. Gastroenterology 117:1397–1407
     [Google Scholar]
  7. Berglund P., Quesada-Rolander M., Putkonen P., Biberfeld G., Thorstensson R., Liljeström P. 1997; Outcome of immunization of cynomolgus monkeys with recombinant Semliki Forest virus encoding human immunodeficiency virus type 1 envelope protein and challenge with a high dose of SHIV-4 virus. AIDS Research and Human Retroviruses 13:1487–1495
     [Google Scholar]
  8. Berglund P., Smerdou C., Fleeton M. N., Tubulekas I., Liljeström P. 1998; Enhancing immune responses using suicidal DNA vaccines. Nature Biotechnology 16:562–565
     [Google Scholar]
  9. Berglund P., Fleeton M. N., Smerdou C., Liljeström P. 1999; Immunization with recombinant Semliki Forest virus induces protection against influenza challenge in mice. Vaccine 17:497–507
     [Google Scholar]
  10. Botarelli P., Brunetto M. R., Minutello M. A., Calvo P., Unutmaz D., Weiner A. J., Choo Q.-L., Shuster J. R., Kuo G., Bonino F., Houghton M., Abrignani S. 1993; T-lymphocyte response to hepatitis C virus in different clinical courses of infection. Gastroenterology 104:580–587
     [Google Scholar]
  11. Brand D., Lemiale F., Turbica I., Buzelay L., Brunet S., Barin F. 1998; Comparative analysis of humoral immune responses to HIV type 1 envelope glycoproteins in mice immunized with a DNA vaccine, recombinant Semliki Forest virus RNA, or recombinant Semliki Forest virus particles. AIDS Research and Human Retroviruses 14:1369–1377
     [Google Scholar]
  12. Brinster C., Inchauspé G. 2001; DNA vaccines for hepatitis C virus. Intervirology 44:143–153
     [Google Scholar]
  13. Brinster C., Muguet S., Lone Y.-C., Boucreux D., Renard N., Fournillier A., Lemonnier F., Inchauspé G. 2001; Different hepatitis C virus nonstructural protein 3 (NS3)-DNA-expressing vaccines induce in HLA-A2.1 transgenic mice stable cytotoxic T lymphocytes that target one major epitope. Hepatology 34:1206–1217
     [Google Scholar]
  14. Calarota S., Wahren B. 2001; Cellular HIV-1 immune responses in natural infection and after genetic immunization. Scandinavian Journal of Infectious Diseases 33:83–96
     [Google Scholar]
  15. Cerny A., McHutchison J. G., Pasquinelli C., Brown M. E., Brothers M. A., Grabscheid B., Fowler P., Houghton M., Chisari F. V. 1995; Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif. Journal of Clinical Investigation 95:521–530
     [Google Scholar]
  16. Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. 1989; Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362
     [Google Scholar]
  17. Choo Q.-L., Weiner A. J., Overby L. R., Kuo G., Houghton M., Bradley D. W. 1990; Hepatitis C virus: the major causative agent of viral non-A, non-B hepatitis. British Medical Bulletin 46:423–441
     [Google Scholar]
  18. Choo Q.-L., Kuo G., Ralston R., Weiner A., Chien D., Van Nest G., Han J., Berger K., Thudium K., Kuo C., Kanposon J., McFarland J., Tabrizi A., Ching K., Moss B., Cummins L. B., Houghton M., Muchmore E. 1994; Vaccination of chimpanzees against infection by the hepatitis C virus. Proceedings of the National Academy of Sciences, USA 91:1294–1298
     [Google Scholar]
  19. Cohen J. 1999; The scientific challenge of hepatitis C. Science 285:26–30
     [Google Scholar]
  20. Colmenero P., Liljeström P., Jondal M. 1999; Induction of P815 tumor immunity by recombinant Semliki Forest virus expressing the P1A gene. Gene Therapy 6:1728–1733
     [Google Scholar]
  21. Colombage G., Hall R., Pavy M., Lobigs M. 1998; DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus. Virology 250:151–163
     [Google Scholar]
  22. Daemen T., Pries F., Bungener L., Kraak M., Regts J., Wilschut J. 2000; Genetic immunization against cervical carcinoma: induction of cytotoxic T lymphocyte activity with a recombinant alphavirus vector expressing human papillomavirus type 16 E6 and E7. Gene Therapy 7:1859–1866
     [Google Scholar]
  23. Davis N. L., Caley I. J., Brown K. W., Betts M. R., Irlbeck D. M., McGrath K. M., Connell M. J., Montefiori D. C., Frelinger J. A., Swanstrom R., Johnson P. R., Johnston R. E. 2000; Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles. Journal of Virology 74:371–378
     [Google Scholar]
  24. Diepolder H. M., Zachoval R., Hoffmann R. M., Wierenga E. A., Santantonio T., Jung M. C., Eichenlaub D., Pape G. R. 1995; Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346:1006–1007
     [Google Scholar]
  25. Diepolder H. M., Gerlach J. T., Zachoval R., Hoffmann R. M., Jung M. C., Wierenga E. A., Scholz S., Santantonio T., Houghton M., Southwood S., Sette A., Pape G. R. 1997; Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. Journal of Virology 71:6011–6019
     [Google Scholar]
  26. Fleeton M. N., Sheahan B. J., Gould E. A., Atkins G. J., Liljeström P. 1999; Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of louping ill virus protect mice from lethal challenge. Journal of General Virology 80:1189–1198
     [Google Scholar]
  27. Fleeton M. N., Liljeström P., Sheahan B. J., Atkins G. J. 2000; Recombinant Semliki Forest virus particles expressing louping ill virus antigens induce a better protective response than plasmid-based DNA vaccines or an inactivated whole particle vaccine. Journal of General Virology 81:749–758
     [Google Scholar]
  28. Gerlach J. T., Diepolder H. M., Jung M.-C., Gruener N. H., Schraut W. W., Zachoval R., Hoffmann R., Schirren C. A., Santantonio T., Pape G. R. 1999; Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C. Gastroenterology 117:933–941
     [Google Scholar]
  29. Glasgow G. M., McGee M. M., Sheahan B. J., Atkins G. J. 1997; Death mechanisms in cultured cells infected by Semliki Forest virus. Journal of General Virology 78:1559–1563
     [Google Scholar]
  30. Grakoui A., Wychowski C., Lin C., Feinstone S. M., Rice C. M. 1993; Expression and identification of hepatitis C virus polyprotein cleavage products. Journal of Virology 67:1385–1395
     [Google Scholar]
  31. Hoofnagle J. H. 1997; Hepatitis C: the clinical spectrum of disease. Hepatology 26 (Suppl. 1):15S–20S
     [Google Scholar]
  32. Inchauspé G., Zebedee S., Lee D.-H., Sugitani M., Nasoff M., Prince A. M. 1991; Genomic structure of the human prototype strain H of hepatitis C virus: comparison with American and Japanese isolates. Proceedings of the National Academy of Sciences, USA 88:10292–10296
     [Google Scholar]
  33. Ishido S., Hotta H. 1998; Complex formation of the nonstructural protein 3 of hepatitis C virus with the p53 tumor suppressor. FEBS Letters 438:258–262
     [Google Scholar]
  34. Kamrud K. I., Hooper J. W., Elgh F., Schmaljohn C. S. 1999; Comparison of the protective efficacy of naked DNA, DNA-based Sindbis replicon, and packaged Sindbis replicon vectors expressing Hantavirus structural genes in hamsters. Virology 263:209–219
     [Google Scholar]
  35. Kanto T., Hayashi N., Takehara T., Tatsumi T., Kuzushita N., Ito A., Sasaki Y., Kasahara A., Hori M. 1999; Impaired allostimulatory capacity of peripheral blood dendritic cells recovered from hepatitis C virus-infected individuals. Journal of Immunology 162:5584–5591
     [Google Scholar]
  36. Kurokohchi K., Akatsuka T., Pendleton C. D., Takamizawa A., Nishioka M., Battegay M., Feinstone S. M., Berzofsky J. A. 1996; Use of recombinant protein to identify a motif-negative human cytotoxic T-cell epitope presented by HLA-A2 in the hepatitis C virus NS3 region. Journal of Virology 70:232–240
     [Google Scholar]
  37. Lamonaca V., Missale G., Urbani S., Pilli M., Boni C., Mori C., Sette A., Massari M., Southwood S., Bertoni R., Valli A., Fiaccadori F., Ferrari C. 1999; Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: implications for vaccine development. Hepatology 30:1088–1098
     [Google Scholar]
  38. Lechner F., Gruener N. H., Urbani S., Uggeri J., Santantonio T., Kammer A. R., Cerny A., Philips R., Ferrari C., Pape G. R., Klenerman P. 2000a; CD8+ T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained. European Journal of Immunology 30:2479–2487
     [Google Scholar]
  39. Lechner F., Wong D. K., Dunbar P. R., Chapman R., Chung R. T., Dohrenwend P., Robbins G., Philips R., Klenerman P., Walker B. D. 2000b; Analysis of a successful immune response in persons infected with hepatitis C virus. Journal of Experimental Medicine 191:1499–1512
     [Google Scholar]
  40. Leitner W. W., Ying H., Restifo N. P. 1999; DNA and RNA-based vaccines: principles, progress and prospects. Vaccine 18:765–777
     [Google Scholar]
  41. Lerat H., Berby F., Trabaud M.-A., Vidalin O., Major M., Trépo C., Inchauspé G. 1996; Specific detection of hepatitis C virus minus strand RNA in hematopoietic cells. Journal of Clinical Investigation 97:845–851
     [Google Scholar]
  42. Liljeström P., Garoff H. 1994; Expression of proteins using Semliki Forest virus vectors. In Current Protocols in Molecular Biology vol 2 pp. 16.20.11–16.20.16 Edited by Ausubel F. M. New York: Wiley Interscience;
     [Google Scholar]
  43. Lodmell D. L., Ray N. B., Parnell M. J., Ewalt L. C., Hanlon C. A., Shaddock J. H., Sanderlin D. S., Rupprecht C. E. 1998; DNA immunization protects nonhuman primates against rabies virus. Nature Medicine 4:949–952
     [Google Scholar]
  44. Loirat D., Lemonnier F. A., Michel M. L. 2000; Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization. Journal of Immunology 165:4748–4755
     [Google Scholar]
  45. Lopez-Dias de Cerio A. L., Casares N., Lasarte J. J., Sarobe P., Perez-Mediavilla L. A., Ruiz M., Prieto J., Borras-Cuesta F. 1999; Th1 but not Th0 cell help is efficient to induce cytotoxic T lymphocytes by immunization with short synthetic peptides. International Immunology 11:2025–2034
     [Google Scholar]
  46. Makimura M., Miyake S., Akino N., Takamori K., Matsuura Y., Miyamura T., Saito I. 1996; Induction of antibodies against structural proteins of hepatitis C virus in mice using recombinant adenovirus. Vaccine 14:28–36
     [Google Scholar]
  47. Morris-Downes M. M., Phenix K. V., Smyth J., Sheahan B. J., Lileqvist S., Mooney D. A., Liljeström P., Todd D., Atkins G. J. 2001; Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems. Vaccine 19:1978–1988
     [Google Scholar]
  48. Mossman S. P., Bex F., Berglund P., Arthos J., O’Neil S. P., Riley D., Maul D. H., Bruck C., Momin P., Burny A., Fultz P. N., Mullins J. I., Liljeström P., Hoover E. A. 1996; Protection against lethal simian immunodeficiency virus SIVsmmPBj14 disease by a recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine. Journal of Virology 70:1953–1960
     [Google Scholar]
  49. Nakano I., Maertens G., Major M. E., Vitvitski L., Dubuisson J., Fournillier A., De Martynoff G., Trepo C., Inchauspé G. 1997; Immunization with plasmid DNA encoding hepatitis C virus envelope E2 antigenic domains induces antibodies whose immune reactivity is linked to the injection mode. Journal of Virology 71:7101–7109
     [Google Scholar]
  50. Nelson D. R., Marousis C. G., Davis G. L., Rice C. M., Wong J., Houghton M., Lau J. Y. N. 1997; The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. Journal of Immunology 158:1473–1481
     [Google Scholar]
  51. Pancholi P., Liu Q., Tricoche N., Zhang P., Perkus M. E., Prince A. M. 2000; DNA prime-canarypox boost with polycistronic hepatitis C virus (HCV) genes generates potent immune responses to HCV structural and nonstructural proteins. Journal of Infectious Diseases 182:18–27
     [Google Scholar]
  52. Pascolo S., Bervas N., Ure J. M., Smith A. G., Lemonnier F. A., Perarnau B. 1997; HLA-A2.1-restricted education and cytolytic activity of CD8+ T lymphocytes from β2 microglobulin (β2m) HLA-A2.1 monochain transgenic H-2D b β2m double knockout mice. Journal of Experimental Medicine 185:2043–2051
     [Google Scholar]
  53. Polack F. P., Lee S. H., Permar S., Manyara E., Nousari H. G., Jeng Y., Mustafa F., Valsamakis A., Adams R. J., Robinson H. L., Griffin D. E. 2000; Successful DNA immunization against measles: neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles. Nature Medicine 6:776–781
     [Google Scholar]
  54. Poynard T., Marcellin P., Lee S., Niederau C., Minuk G. S., Ideo G., Bain V., Heathcore J., Zeuzem S., Trepo C., Albrecht J. 1998; Randomised trial of interferon α2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 352:1426–1432
     [Google Scholar]
  55. Prezzi C., Casciaro M. A., Francavilla V., Schiaffella E., Finocchi L., Chircu L. V., Bruno G., Sette A., Abrignani S., Barnaba V. 2001; Virus-specific CD8+ T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection. European Journal of Immunology 31:894–906
     [Google Scholar]
  56. Pugachev K. V., Mason P. W., Shope R. E., Frey T. K. 1995; Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of Japanese encephalitis virus induce significant protection in mice against lethal JEV infection. Virology 212:587–594
     [Google Scholar]
  57. Reddy J. R., Kwang J., Varthakavi V., Lechtenberg K. F., Minocha H. C. 1999; Semliki forest virus vector carrying the bovine viral diarrhea virus NS3 (p80) cDNA induced immune responses in mice and expressed BVDV protein in mammalian cells. Comparative Immunology Microbiology and Infectious Diseases 22:231–246
     [Google Scholar]
  58. Rehermann B., Chang K.-M., McHutchison J., Kokka R., Houghton M., Rice C. M., Chisari F. V. 1996; Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. Journal of Virology 70:7092–7102
     [Google Scholar]
  59. Robinson H. L., Montefiori D. C., Johnson R. P., Manson K. H., Kalish M. L., Lifson J. D., Rizvi T. A. and others 1999; Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nature Medicine 5:526–534
     [Google Scholar]
  60. Saito I., Miyamura T., Ohbayashi A., Harada H., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji M., Ohta Y., Choo Q., Houghton M., Kuo G. 1990; Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proceedings of the National Academy of Sciences, USA 87:6547–6549
     [Google Scholar]
  61. Sakamuro D., Furukawa T., Takegami T. 1995; Hepatitis C virus non structural protein NS3 transforms NIH 3T3 cells. Journal of Virology 69:3893–3896
     [Google Scholar]
  62. Schlesinger S., Schlesinger M. J. 1996; Togaviridae : the viruses and their replication. In Fields Virology pp 825–841 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
     [Google Scholar]
  63. Shirai M., Akatsura T., Pendleton C. D., Houghten R., Wychowski C., Mihalik K., Feinstone S., Berzofsky J. A. 1992; Induction of cytotoxic T cells to a cross-reactive epitope in the hepatitis C virus nonstructural RNA polymerase-like protein. Journal of Virology 66:4098–4106
     [Google Scholar]
  64. Shoji I., Suzuki T., Sato M., Aizaki H., Chiba T., Matsuura Y., Miyamura T. 1999; Internal processing of hepatitis C virus NS3 protein. Virology 254:315–323
     [Google Scholar]
  65. Smerdou C., Liljeström P. 1999; Two-helper RNA system for production of recombinant Semliki Forest virus particles. Journal of Virology 73:1092–1098
     [Google Scholar]
  66. Tsuji M., Bergmann C. C., Takita-Sonoda Y., Murata K.-I., Rodrigues E. G., Nussenzweig R. S., Zavala F. 1998; Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a malaria parasite or of influenza virus elicit protection against the corresponding pathogen in mice. Journal of Virology 72:6907–6910
     [Google Scholar]
  67. Wedemeyer H., Gagneten S., Davis A. R., Feinstone S. M., Rehermann B. 2000; Oral immunization with HCV-NS3 encoding salmonella: long-lasting induction of HCV-specific CTL in an HLA-A2 transgenic mouse model. Hepatology 32:905
     [Google Scholar]
  68. Woodberry T., Gardner J., Mateo L., Eisen D., Medvecsky J., Ramshaw I. A., Thomson S. A. and others 1999; Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8+ cytotoxic T-cell epitopes. Journal of Virology 73:5320–5325
     [Google Scholar]
  69. Ying H., Zaks T. Z., Wang R.-F., Irvine K. R., Kammula U. S., Marincola F. M., Leitner W. W., Restifo N. P. 1999; Cancer therapy using a self-replicating RNA vaccine. Nature Medicine 5:823–827
     [Google Scholar]
  70. Zhou J., Berglund P., Zhao H., Liljeström P., Jondal M. 1995; Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus. Proceedings of the National Academy of Sciences, USA 72:3009–3013
     [Google Scholar]
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Hepatitis C virus non-structural protein 3-specific cellular immune responses following single or combined immunization with DNA or recombinant Semliki Forest virus particles
J. Gen. Virol. 83, 369 (2002); https://doi.org/10.1099/0022-1317-83-2-369
/content/journal/jgv/10.1099/0022-1317-83-2-369
/content/journal/jgv/10.1099/0022-1317-83-2-369
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