1887

Abstract

High yielding adenovirus (Ad)-hepatitis B recombinant (Ad-Hep B) viruses were prepared by insertion of the hepatitis B surface antigen (HBsAg) gene into the early region 3 (E3 region) of Ad4 or Ad7 vectors containing intact or largely deleted E3 regions. Both E3-deleted and non-deleted recombinants produced about six- to eightfold higher amounts of HBsAg than previously reported recombinants. These recombinant viruses were evaluated for immunogenicity in dogs which sustain abortive lung infections by Ad4 and Ad7. Recombinants containing E3 deletions elicited 10- to 12-fold stronger anti- HBs primary responses than previously evaluated low yield recombinants. Further immunizations with heterotypic Ad-Hep B recombinants induced substantial anti-HBs booster responses as well as anti-‘a’ epitope responses. In contrast, recombinant viruses containing intact E3 regions induced only weak or negligible anti- HBs responses, although such viruses induced strong antibody responses to the Ad vectors. The immunogenicity of high-yielding Ad recombinants correlated with temporal expression of HBsAg and thus the dog represents a valuable model for evaluation of immune responses to heterologous proteins that are expressed early and that do not require efficient DNA replication. Recombinants expressing HBsAg late in the infectious cycle require further testing in the fully permissive chimpanzee model. This study establishes that the E3- deleted high yield Ad4 and Ad7 recombinants represent promising live oral hepatitis B vaccine candidates.

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1994-01-01
2022-01-17
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References

  1. Berkner K. L. 1988; Development of adenovirus vectors for the expression of heterologous genes. Biotechniques 6:616–629
    [Google Scholar]
  2. Bhat B. M., Wold W. S. M. 1986; Genetic analysis of mRNA synthesis in region E3 of adenovirus at different stages of productive infection by RNA processing mutants. Journal of Virology 60:54–63
    [Google Scholar]
  3. Bhat B. M., Brady H. A., Pursley M. H., Wold W. S. M. 1986; Deletion mutants that alter the differential RNA processing in E3 complex transcription unit of adenovirus. Journal of Molecular Biology 190:543–557
    [Google Scholar]
  4. Bhatnagar P. K., Papas E., Blum H. E., Milich D. R., Nitecki D., Karels M. J., Vyas G. N. 1982; Immune response to synthetic peptide analogues of hepatitis B surface antigen specific for the ‘a’ determinant. Proceedings of the National Academy of Sciences U.S.A.: 794400–4404
    [Google Scholar]
  5. Burgert H-G, Maryanski J. L., Kvist S. 1987; ‘E3/19K’ protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell-surface expression of histocompatibility class I antigens. Proceedings of the National Academy of Sciences U.S.A.: 841356–1360
    [Google Scholar]
  6. Carlin C. R., Tollefson A. E., Brady H. A., Hoffman B. L., Wold W. S. M. 1989; Epidermal growth factor receptor is downregulated by 10,400 MW protein encoded by the E3 region of adenovirus. Cell 57:135–144
    [Google Scholar]
  7. Chengalvala M., Lubeck M. D., Selling B. J., Natuk R. J., Hsu K.-H., Mason B. B., Chanda P. K., Bhat B. M., Mizutani S., Davis A. R., Hung P. P. 1991a; Adenovirus vectors for gene expression. Current Opinion in Biotechnology 2:718–722
    [Google Scholar]
  8. Changalvala M., Lubeck M. D., Davis A. R., Mizutani S., Molnar-Kimber K., Morin J., Hung P. P. 1991b; Evaluation of adenovirus type 4 and 7 recombinant hepatitis B vaccines in dogs. Vaccine 9:485–490
    [Google Scholar]
  9. Dewar R. L., Natarajan V., Vasudevachari M. B., Salzman N. P. 1989; Synthesis and processing of human immunodeficiency virus type 1 envelope proteins encoded by a recombinant human adenovirus. Journal of Virology 63:129–136
    [Google Scholar]
  10. Ginsberg H. S., Lundholm-Beauchamp U., Horswood R. L., Pernis B., Wold W. S. M., Chanock R. M., Prince G. A. 1989; Role of early region 3 (E3) in pathogenesis of adenovirus disease. Proceedings of the National Academy of Sciences U.S.A.: 863823–3827
    [Google Scholar]
  11. Haz-Ahmed Y., Graham F. L. 1986; Development of a helper- independent human adenovirus vector and its use in the transfer of herpes simplex virus thymidine kinase gene. Journal of Virology 57:267–274
    [Google Scholar]
  12. Hjorth R. N., Bonde G. M., Perzchala W. A., Vernon S. K., Wiener F. P., Levner M. H., Lubeck M. D., Hung P. P. 1988; A new hamster model for adenovirus vaccination. Archives of Virology 100:279–283
    [Google Scholar]
  13. Iwarson S., Tabor E., Thomas H. C., Goodall A., Waters J., Sony P., Shih J. W., Gerety R. J. 1985; Neutralization of hepatitis B virus infectivity by a murine monoclonal antibody: an experimental study in chimpanzee. Journal of Medical Virology 16:89–96
    [Google Scholar]
  14. Johnson D. C. 1991; Adenovirus vectors as potential vaccines against herpes simplex virus. Reviews of Infectious Diseases 13:s912–s916
    [Google Scholar]
  15. Kozak M. 1978; How do eukaryotic ribosomes select initiation regions in messenger RNA?. Cell 15:1109–1123
    [Google Scholar]
  16. Logan J., Shenk T. 1984; Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection. Proceedings of the National Academy of Sciences U.S.A.: 813655–3659
    [Google Scholar]
  17. Lubeck M. D., Davis A. R., Chengalvala M., Natuk R. J., Morin J. E., Molnar-Kimber K., Mason B. B., Bhat B. M., Mizutani S., Hung P. P., Purcell R. H. 1989; Immuno-genicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus. Proceedings of the National Academy of Sciences U.S.A.: 866763–6767
    [Google Scholar]
  18. Marshall G. S., Ricciardi R. P., Rando R. F., Puck J., Ge R., Plotkin S. A., Gönczöl E. 1990; An adenovirus recombinant that expresses the human cytomegalovirus major envelope glycoprotein and induces neutralizing antibodies. Journal of Infectious Diseases 762:1177–1181
    [Google Scholar]
  19. Mason B. B., Davis A. R., Bhat B. M., Chengalvala M., Lubeck M. D., Zandle G., Kostek B., Cholodofsky S., Dheer S. K., Molnar-Kimber K., Mizutani S., Hung P. P. 1990; Adenovirus vaccine vectors expressing hepatitis B surface antigen: importance of regulatory elements in the adenovirus major late intron. Virology 177:452
    [Google Scholar]
  20. Molnar-Kimber K. L., Jarocki-Witek V., Dheer S. K., Vernon S. K., Conley A. J., Davis A. R., Hung P. P. 1988; Distinctive properties of the hepatitis B virus envelope proteins. Journal of Virology 62:407–416
    [Google Scholar]
  21. Morin J. E., Lubeck M. D., Barton J. E., Conley A. J., Davis A. R., Hung P. P. 1987; Recombinant adenovirus induces antibody response to hepatitis B virus surface antigen in hamsters. Proceedings of the National Academy of Sciences U.S.A.: 844626–4630
    [Google Scholar]
  22. Morin J. E., Lubeck M. D., Mason B. B., Molnar-Kimber K. L., Dheer S. K., Bhat B. M., Chanda P. K., Natuk R. J., Chengalvala M., Mizutani S., Davis A. R., Hung P. P. 1990; Recombinant adenovirus vaccines for hepatitis B virus. In New Generation Vaccines pp 448–457 Woodrow G. C., Levine M. M. Edited by New York: Marcel Dekker;
    [Google Scholar]
  23. Pacini D. L., Dubovi E. J., Clyde W. A.Jr 1984; A new animal model for human respiratory tract disease due to adenovirus. Journal of Infectious Diseases 150:92–97
    [Google Scholar]
  24. Prevec L., Schneider M., Rosenthal K. L., Belbeck L. W., Derbyshire J. B., Graham F. L. 1989; Use of human adenovirus-based vectors for antigen expression in animals. Journal of General Virology 70:429–434
    [Google Scholar]
  25. Schneider M., Graham F. L., Prevec L. 1989; Expression of the glycoprotein of vesicular stomatitis virus by infectious adenovirus vectors. Journal of General Virology 70:417–427
    [Google Scholar]
  26. Tikchonenko T. I. 1989; Adenoviruses as vectors for the transfer of genetic information and for the construction of new type vaccines. Advances in Experimental Medicine and Biology 257:193–204
    [Google Scholar]
  27. Tollefson A. E., Steward A. R., Yei S., Saha S. K., Wold W. S. M. 1991; The 10,400- and 14,500-dalton proteins encoded by region E3 of adenovirus form a complex and function together to down-regulate the epidermal growth factor receptor. Journal of Virology 65:3095–3105
    [Google Scholar]
  28. Top F. H., Buescher E. L., Bancroft W. H., Russell P. K. 1971; Immunization with live types 7 and 4 adenovirus vaccines. II. Antibody response and protective effect against acute respiratory disease due to an adenovirus type 7. Journal of Infectious Diseases 124:155–160
    [Google Scholar]
  29. Wold W. M., Gooding L. R. 1991; Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology 184:1–8
    [Google Scholar]
  30. Wold W. S. M., Cladaras C., Deutscher S. L., Kapoor Q. S. 1985; The 19K glycoprotein encoded by region E3 of adenovirus. Journal of Biological Chemistry 260:2424–2431
    [Google Scholar]
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