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Co-expression of hepatitis B virus antigens by a non-defective adenovirus vaccine vector

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Summary

Adenovirus type 7 vaccine strain was engineered to express foreign antigens from both the E 3 early promoter in the E 3 region and the major late promoter inserted between the E 4 region and the right inverted terminal repeat. This multiple expression vector was used to express hepatitis B core antigen (HBcAg), hepatits B e antigen (HBeAg), and hepatitis B surface antigen (HBsAg). The gene inserted in the E 3 region was derived from the core gene of the hepatitis B virus genome. When the precore region was present, an immunoreactive group of proteins with molecular weights ranging from 15,000 to 19,000 was secreted into the media. Velocity sedimentation centrifugation of media and lysates from cells infected with recombinants containing the core gene with the precore region resulted in peaks of HBeAg at the top of the gradient where authentic HBeAg should be found. In addition to the core gene in the E 3 region, the surface antigen gene of hepatitis B virus was inserted behind the major late promoter in the E 4 region resulting in an adeno-hepatitis recombinant virus capable of expressing both the core gene and the HBsAg cells. Cells infected with the adeno-hepatitis recombinants could also be stained with peroxidase-conjugates after reacting to antibody against HBcAg. Inoculation of dogs with the recombinant viruses which contained the core gene, with and without the precore sequence, resulted in a significant antibody response to HBcAg/HBeAg. The dogs also produced a significant antibody response to HBsAg as well as neutralizing antibody to adenovirus.

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References

  1. Araki K, Miyazaki J, Hino N, Tomita N, Chisaka O, Matsubara K, Yamamura K (1989) Expression and replication of hepatitis B virus genome in transgenic mice. Proc Natl Acad Sci USA 86: 207–211

    Google Scholar 

  2. Berkner KL, Sharp PA (1983) Generation of adenovirus by transfection of plasmids. Nucleic Acids Res 11: 6003–6020

    Google Scholar 

  3. Bruss V, Gerlich WH (1988) Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. Virology 163: 268–275

    Google Scholar 

  4. Burnette WN (1981) Western blotting: electrophoretic transfer of protein from sodium dodecyl sulfate — polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibodies and radioiodinated protein A. Anal Biochem 112: 195–203

    Google Scholar 

  5. Celis E, Ou D, Otvos Jr L (1988) Recognition of hepatitis B surface antigen by human T lymphocytes: proliferative and cytotoxic responses to a major antigenic determinant defined by synthetic peptides. J Immunol 140: 1808–1815

    Google Scholar 

  6. Cheng SM, Vogel R, Ye W, Blume M, Lee S, Hung P (1988) The core gene of hepatitis B virus; subtype adw2. Nucleic Acids Res 16: 8188

    Google Scholar 

  7. Clarke BE, Newton SE, Carroll AR, Francis MH, Appleyard G, Syred AD, Highfield PE, Rowlands DJ, Brown F (1987) Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein. Nature 330: 381–383

    Google Scholar 

  8. Colucci G, Beazer Y, Cataluppi C, Tackney C (1988) Identification of a major hepatitis B core antigen (HBcAg) determinant by using synthetic peptides and monoclonal antibodies. J Immunol 141: 4376–4380

    Google Scholar 

  9. Davis AR, Kostek B, Mason BB, Hsiao CL, Morin J, Dheer SK, Hung PP (1985) Expression of hepatitis B surface antigen with a recombinant adenovirus. Proc Natl Acad Sci USA 82: 7560–7564

    Google Scholar 

  10. Dewar RL, Natarajan V, Vasudevachari MB, Salzman NP (1989) Synthesis and processing of human immunodeficiency virus type 1 envelope proteins of human immunodeficiency virus type 1 envelope proteins encoded by a recombinant human adenovirus. J Virol 63: 129–136

    Google Scholar 

  11. Ferrari F, Chisari V, Ribera E, Penna A, Mondelli MU (1988) Functional modulation of hepatitis B core antigen-specific T-lymphocytes by an autoreactive T-cell clone. J Immunol 141: 1155–1160

    Google Scholar 

  12. Garcia PD, Ou J-C, Rutter WJ, Walter P (1988) Targeting of the hepatitis B virus precore protein of the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. J Cell Biol 160: 1093–1104

    Google Scholar 

  13. Hanahan D, Gluzman Y (1984) Rescue of functional replication origins from embedded configurations in a plasmid carrying the adenovirus genome. Mol Cell Biol 4: 302–309

    Google Scholar 

  14. Hirt B (1967) Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol 26: 365–369

    Google Scholar 

  15. Iwarson S, Tabor E, Thomas HC, Gerety RJ (1985) Protection against hepatitis B virus infection by immunization with hepatitis B core antigen. Gastroenterology 88: 763–767

    Google Scholar 

  16. Jean-Jean O, Levrero M, Will H, Perricaudet M, Rossignol J (1989) Expression mechanism of the hepatitis B virus (HBV) gene. Virology 170: 99–106

    Google Scholar 

  17. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T 4. Nature 227: 680–685

    Google Scholar 

  18. Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G (1976) A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer 17: 62–70

    Google Scholar 

  19. Logan J, Shenk T (1984) Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection. Proc Natl Acad Sci USA 81: 3655–3659

    Google Scholar 

  20. Lubeck MD, Davis AR, Chengalvala M, Morin JE, Molnar-Kimber K, Natuk R, Mason BB, Mizutani S, Hung PP, Purcell RH (1989) Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based upon live recombinant adenovirus. Proc Natl Acad Sci USA 86: 6763–6767

    Google Scholar 

  21. Mason BB, Davis AR, Bhat BM, Chengalvala M, Lubeck MD, Zandle G, Kostek B, Cholodofsky S, Dheer S, Molnar-Kimber K, Mizutani S, Hung PP (1990) Adenovirus vaccine vectors expressing hepatitis B surface antigen: importance of regulatory elements in the adenovirus major late intron. Virology 177: 452–461

    Google Scholar 

  22. Matsuda K, Ohori I (1988) Immunochemical characteristics of hepatitis B e antigen subspecificities, HBeAg/1 and HBeAg/2. J Immunol 141: 1709–1713

    Google Scholar 

  23. McLachlan A, Milich DR, Raney AK, Riggs RW, Hughes JL, Sorgi J, Chisari FV (1987) Expression of hepatitis B virus surface and core antigens: influences of pre-S and precore sequences. J Virol 61: 683–692

    Google Scholar 

  24. Milich DR, McNamara MK, McLachlan A, Thronton GB, Chisari FV (1985) Distinct H-2-linked regulation of T-cell responses to the pre-S and S regions of the same hepatitis B surface antigen polypeptide allows circumvention of nonresponsiveness to the S region. Proc Natl Acad Sci USA 82: 8168–8172

    Google Scholar 

  25. Milich DR, McLachlan A, Thornton GB, Hughes JL (1987) Antibody production of the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T-cell site. Nature 329: 547–549

    Google Scholar 

  26. Milich DR, McLachlan A, Moriarty A, Thornton GB (1987) Immune response to hepatitis B virus core antigen (HBcAg): localization of T-cell recognition sites within HBcAg/HBeAg. J Immunol 139: 1223–1231

    Google Scholar 

  27. Milich DR (1988) T- and B-cell recognition of hepatitis B viral antigens. Immunol Today 9: 380–386

    Google Scholar 

  28. Miyanohara A, Imamura T, Araki M, Sugawara K, Ohtomo N, Matsubara K (1986) Expression of hepatitis B virus core antigen gene inSaccaromyces cerevisiae: synthesis of two poly-peptides translated from different initiation codons. J Virol 59: 176–180

    Google Scholar 

  29. Molnar-Kimber KL, Jarock-Witek V, Dheer SK, Vernon SK, Conley AJ, Davis AR, Hung PP (1988) Distinctive properties of hepatitis B virus envelope proteins. J Virol 62: 407–416

    Google Scholar 

  30. Morin JE, Lubeck MD, Barton JE, Conley AJ, Davis AR, Hung PP (1987) Recombinant adenovirus induces antibody response to hepatitis B surface antigen in hamsters. Proc Natl Acad Sci USA 84: 4626–4630

    Google Scholar 

  31. Murray K, Bruce SA, Wingfield P, Van Eerd P, De Reus A, Schellenkens H (1987) Protective immunization against hepatitis B with an internal antigen of the virus. J Med Virol 23: 101–107

    Google Scholar 

  32. Ohori H, Matsuda K (1989) Intra- and extracellular distribution and immunochemical characterization of hepatitis B virus nucleocapsid proteins produced by a human hepatoma cell line transfected with cloned viral DNA. Virology 168: 40–47

    Google Scholar 

  33. Ou J-H, Laub O, Retter WJ (1986) Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci USA 83: 1578–1582

    Google Scholar 

  34. Ou J-H, Bell KD (1990) Comparative studies of hepatitis B virus precore and core particles. Virology 174: 185–191

    Google Scholar 

  35. Prevec L, Schneider M, Rosenthal KL, Belbeck LW, Derbyshire JB, Graham FL (1989) Use of human adenovirus-based vectors for antigen expression in animals. J Gen Virol 70: 429–434

    Google Scholar 

  36. Rouse BJ, Norley S, Martin S (1988) Antiviral cytotoxic T lymphocyte induction and vaccination. Rev Infect Dis 10: 16–33

    Google Scholar 

  37. Salfeld J, Pfaff E, Noah N, Schaller H (1989) Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus. J Virol 63: 798–808

    Google Scholar 

  38. Schneider M, Graham FL, Prevec L (1989) Expression of the glycoprotein of vesicular stomatitis virus by infectious adenovirus vectors. J Gen Virol 70: 417–427

    Google Scholar 

  39. Scolnick EA, McLean AA, West DJ, McAller WJ, Miller WJ, Buynak EB (1984) Clinical evaluation in healty adults of a hepatitis B vaccine made by recombinant DNA. JAMA 251: 2812–2815

    Google Scholar 

  40. Spessot R, Inchley K, Hupel TM, Bacchetti S (1989) Cloning of the herpes simplex virus ICP4 gene in an adenovirus vector: effects on adenovirus gene expression and replication. Virology 168: 378–387

    Google Scholar 

  41. Standring DN, Ou J-H, Rutter J (1986) Assembly of viral particles inXenopus oocytes: pre-surface-antigens regulate secretion of the hepatitis B viral surface envelope particle. Proc Natl Acad Sci USA 83: 9338–9342

    Google Scholar 

  42. Standring DN, Ou J-H, Masiarn FR, Butler WJ (1988) A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogenous population of e antigens inXenopus oocytes. Proc Natl Acad Sci USA 85: 8405–8409

    Google Scholar 

  43. Suzuki K, Uchida T, Houicha R, Shikata T (1985) Localization of hepatitis B surface and core antigens in human hepatocellular carcinoma by immunoperoxidase methods. Cancer 56: 321–327

    Google Scholar 

  44. Tabor E, Gerety RJ (1984) Possible role of immune responses to hepatitis B core antigen in protection against hepatitis B infections. Lancet i: 172

    Google Scholar 

  45. Takehara K, Ireland D, Bishop DHL (1988) Co-expression of the hepatitis B surface and core antigens using bacculovirus multiple expression vectors. J Gen Virol 69: 2763–2777

    Google Scholar 

  46. Top FH Jr (1975) Control for adenovirus acute respiratory disease in U.S. army trainees. Yale J Biol Med 48: 185–195

    Google Scholar 

  47. Top FH Jr, Buescher EL, Bancroft WH, Russell PK (1971) Immunization with live types 7 and 4 adenovirus vaccine II antibody response disease due to adenovirus type 7. J Infect Dis 124: 155–160

    Google Scholar 

  48. Weiner J, Solfeld J, Will H (1987) Expression of the hepatitis B virus core gene in vitro and in vivo. J Virol 61: 3109–3113

    Google Scholar 

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Author notes

  1. Wei Wei Ye

    Present address: Laboratory of Tumor Cell BiologyLaboratory of Tumor Cell BiologyLaboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland, USA

Authors and Affiliations

  1. Wyeth-Ayerst Research, Biotechnology and Microbiology Division, Philadelphia, Pennsylvania, USA

    Wei Wei Ye, B. B. Mason, Murty Chengalvala, Sheau-Mei Cheng, G. Zandle, M. D. Lubeck, Shaw-Guang Lee, Satoshi Mizutani, A. R. Davis & P. P. Hung

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  1. Wei Wei Ye
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  2. B. B. Mason
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  3. Murty Chengalvala
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  4. Sheau-Mei Cheng
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  5. G. Zandle
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  6. M. D. Lubeck
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  7. Shaw-Guang Lee
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Ye, W.W., Mason, B.B., Chengalvala, M. et al. Co-expression of hepatitis B virus antigens by a non-defective adenovirus vaccine vector. Archives of Virology 118, 11–27 (1991). https://doi.org/10.1007/BF01311300

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  • DOI: https://doi.org/10.1007/BF01311300

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