1887

Abstract

An effective vaccine against infection with human immunodeficiency virus type 1 (HIV-1) is thought likely to require both a humoral and a CTL immune response. A non-replicating adenovirus vector system has been developed that can induce both a humoral and CTL response to HIV-1 envelope in mice. It is demonstrated that the stimulatory / 5′ splice-donor site sequence is required for efficient expression of HIV-1 by this adenovirus vector system. can be provided bicistronically or to result in good expression of . A humoral immune response was detected after two immunizations with a bicistronic recombinant adenovirus (RAd142). The response was dose dependent, 5×10 p.f.u. inducing a response in some, but not all, animals and 1×10 p.f.u. giving a consistent antibody response. However, CTLs were induced by the lower dose of virus and after only one immunization with the higher dose. A positive CTL response was also seen consistently when the two monocistronic adenoviruses (RAd501 expressing and RAd46 expressing ) were given together, although two immunizations were required to give approximately the same level of response as seen with the bicistronic virus. RAd501 on its own also gave a low CTL response when two immunizations were given. It is suggested that a lower level of expression is required to produce a CTL response than a humoral response and that this non- replicating adenovirus vector is a good system for inducing CTL.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-10-2621
1999-10-01
2020-11-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/10/0802621a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-10-2621&mimeType=html&fmt=ahah

References

  1. Arya S. K., Guo C., Josephs S. F., Wong-Staal F.. 1985; Trans -activator gene of human T-lymphotropic virus type III (HTLV-III. Science229:69–73
    [Google Scholar]
  2. Barksdale S. K., Baker C. C.. 1995; The human immunodeficiency virus type 1 Rev protein and the Rev-responsive element counteract the effect of an inhibitory 5′ splice site in a 3′ untranslated region. Molecular and Cellular Biology15:2962–2971
    [Google Scholar]
  3. Chanda P. K., Natuk R. J., Mason B. B., Bhat B. M., Greenberg L., Dheer S. K., Molnar-Kimber K. L., Mizutani S., Lubeck M. D., Davis A. R., Hung P. P.. 1990; High level expression of the envelope glycoproteins of the human immunodeficiency virus type I in presence of rev gene using helper-independent adenovirus type 7 recombinants. Virology175:535–547
    [Google Scholar]
  4. Chang D. D., Sharp P. A.. 1989; Regulation by HIV Rev depends upon recognition of splice sites. Cell59:789–795
    [Google Scholar]
  5. Chenciner N., Randrianarison-Jewtoukoff V., Delpeyroux F., Hanania N., Pedroza Martins L., Stratford Perricaudet L., Perricaudet M., Wain-Hobson S.. 1997; Enhancement of humoral immunity to SIVenv following simultaneous inoculation of mice by three recombinant adenoviruses encoding SIVenv/poliovirus chimeras. Tat and Rev. AIDS Research and Human Retroviruses13:801–806
    [Google Scholar]
  6. 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 Virology63:129–136
    [Google Scholar]
  7. Emerman M., Vazeux R., Peden K.. 1989; The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell57:1155–1165
    [Google Scholar]
  8. Feinberg M. B., Jarrett R. F., Aldovini A., Gallo R. C., Wong-Staal F.. 1986; HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell46:807–817
    [Google Scholar]
  9. Flanagan B., Pringle C. R., Leppard K. N.. 1997; A recombinant human adenovirus expressing the simian immunodeficiency virus Gag antigen can induce long-lived immune responses in mice. Journal of General Virology78:991–997
    [Google Scholar]
  10. Fooks A. R., Schadeck E., Liebert U. G., Dowsett A. B., Rima B. K., Steward M., Stephenson J. R., Wilkinson G. W. G.. 1995; High-level expression of the measles virus nucleocapsid protein by using a replication-deficient adenovirus vector: induction of an MHC-1- restricted CTL response and protection in a murine model. Virology210:456–465
    [Google Scholar]
  11. Fooks A. R., Jeevarajah D., Lee J., Warnes A., Niewiesk S., ter Meulen V., Stephenson J. R., Clegg J. C. S.. 1998; Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents. Journal of General Virology79:1027–1031
    [Google Scholar]
  12. Graham F. L., Smiley J., Russell W. C., Nairn R.. 1977; Characteristics of a human cell line transformed by DNA from human adenovirus type 5. Journal of General Virology36:59–74
    [Google Scholar]
  13. Hammarskjold M.-L., Li H., Rekosh D., Prasad S.. 1994; Human immunodeficiency virus env expression becomes Rev-independent if the env region is not defined as an intron. Journal of Virology68:951–958
    [Google Scholar]
  14. Hanke T., Schneider J., Gilbert S. C., Hill A. V. S., McMichael A.. 1998a; DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum : immunogenicity in mice. Vaccine16:426–435
    [Google Scholar]
  15. Hanke T., Blanchard T. J., Schneider J., Hannan C. M., Becker M., Gilbert S. C., Hill A. V. S., Smith G. L., McMichael A.. 1998b; Enhancement of MHC class I- restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime. Vaccine16:439–445
    [Google Scholar]
  16. Imler J.-L.. 1995; Adenovirus vectors as recombinant viral vaccines. Vaccine13:1143–1151
    [Google Scholar]
  17. Jacobs S. C., Stephenson J. R., Wilkinson G. W. G.. 1992; High- level expression of the tick-borne encephalitis virus NS1 protein by using an adenovirus-based vector: protection elicited in a murine model. Journal of Virology66:2086–2095
    [Google Scholar]
  18. Jones D. H., McBride B. W., Roff M. A., Farrar G. H.. 1995; Efficient purification and rigorous characterisation of a recombinant gp120 for HIV vaccine studies. Vaccine13:991–999
    [Google Scholar]
  19. Juillard V., Villefroy P., Godfrin D., Pavirani A. M., Venet A., Guillet J.-G.. 1995; Long-term humoral and cellular immunity induced by a single immunization with replication-defective adenovirus recombinant vector. European Journal of Immunology25:3467–3473
    [Google Scholar]
  20. Kjems J., Sharp P. A.. 1993; The basic domain of Rev from human immunodeficiency virus type 1 specifically blocks the entry of U4/U6.U5 small nuclear ribonucleoprotein in spliceosome assembly. Journal of Virology67:4769–4776
    [Google Scholar]
  21. Lu X. B., Heimer J., Rekosh D., Hammarskjold M.-L.. 1990; U1 small nuclear RNA plays a direct role in the formation of a rev -regulated human immunodeficiency virus env mRNA that remains unspliced. Proceedings of the National Academy of Sciences, USA87:7598–7602
    [Google Scholar]
  22. Lubeck M. D., Natuk R. J., Chengalvala M., Chanda P. K., Murthy K. K., Murthy S., Mizutani S., Lee S.-G., Wade M. S., Bhat B. M., Bhat R., Dheer S. K., Eichberg J. W., Davis A. R., Hung P. P.. 1994; Immunogenicity of recombinant adenovirus–human immunodeficiency virus vaccines in chimpanzees following intranasal administration. AIDS Research and Human Retroviruses10:1443–1449
    [Google Scholar]
  23. McGrory W. J., Bautista D. S., Graham F. L.. 1988; A simple technique for the rescue of early region I mutations into infectious human adenovirus type 5. Virology163:614–617
    [Google Scholar]
  24. Mikaelian I., Krieg M., Gait M. J., Karn J.. 1996; Interactions of INS (CRS) elements and the splicing machinery regulate the production of Rev-responsive mRNAs. Journal of Molecular Biology257:246–264
    [Google Scholar]
  25. Nasioulas G., Zolotukhin A. S., Tabernero C., Solomin L., Cunningham C. P., Pavlakis G. N., Felber B. K.. 1994; Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA. Journal of Virology68:2986–2993
    [Google Scholar]
  26. Natuk R. J., Chanda P. K., Lubeck M. D., Davis A. R., Wilhelm J., Hjorth R., Wade M. S., Bhat B. M., Mizutani S., Lee S., Eichberg J., Gallo R. C., Hung P. P., Robert-Guroff M.. 1992; Adenovirus–human immunodeficiency virus (HIV) envelope recombinant vaccines elicit high- titered HIV-neutralizing antibodies in the dog model. Proceedings of the National Academy of Sciences, USA89:7777–7781
    [Google Scholar]
  27. Natuk R. J., Lubeck M. D., Chanda P. K., Chengalvala M., Wade M. S., Murthy S. C. S., Wilhelm J., Vernon S. K., Dheer S. K., Mizutani S., Lee S.-G., Murthy K. K., Eichberg J. G., Davis A. R., King P. P.. 1993; Immunogenicity of recombinant human adenovirus–human immunodeficiency virus vaccines in chimpanzees. AIDS Research and Human Retroviruses9:395–404
    [Google Scholar]
  28. Polyanskaya N., Sharpe S., Cook N., Leech S., Banks J., Dennis M., Hall G., Stott J., Cranage M. P.. 1997; Anti-major histocompatibility complex antibody responses to simian B cells do not protect macaques against SIVmac infection. AIDS Research and Human Retroviruses13:923–931
    [Google Scholar]
  29. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. J., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K., Ivanoff L., Petteway S. R. Jr, Pearson M. L., Lautenberger J. A., Papas T. S., Ghrayeb J., Chang N. T., Gallo R. C., Wong-Staal F.. 1985; Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature313:277–284
    [Google Scholar]
  30. Rosen C. A., Terwilliger E., Dayton A. I., Sodroski J. G., Haseltine W. A.. 1988; Intragenic cis -acting art gene-responsive sequences of the human immunodeficiency virus. Proceedings of the National Academy of Sciences, USA85:2071–2075
    [Google Scholar]
  31. Sambrook J., Fritsch E. F., Maniatis T.. 1989; Molecular Cloning: A Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  32. Sodroski J., Goh W. C., Rosen C. A., Dayton A., Terwilliger E., Haseltine W. A.. 1986; A second post- transcriptional trans -activator gene required for HTLV-III replication. Nature321:412–417
    [Google Scholar]
  33. Takahashi H., Nakagawa Y., Yokomuro K., Berzofsky J. A.. 1993; Induction of CD8 + cytotoxic T lymphocytes by immunization with syngeneic irradiated HIV-1 envelope derived peptide-pulsed dendritic cells. International Immunology5:849–857
    [Google Scholar]
  34. Van Beveren C., Coffin J., Hughes S.. 1985; HTLV-3 genome. In RNA Tumor Viruses , 2nd edn. Supplements and Appendices pp1109–1123 Edited by Weiss R., Teich N., Coffin J. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  35. Wilkinson G. W. G.. 1994; Gene therapy and viral vaccination. Reviews in Medical Microbiology5:97–106
    [Google Scholar]
  36. Wilkinson G. W. G., Akrigg A.. 1992; Constitutive and enhanced expression from the CMV major IE promoter in a defective adenovirus vector. Nucleic Acids Research20:2233–2239
    [Google Scholar]
  37. Zhang W. W., Fang X., Branch C. D., Mazur W., French B. A., Roth J. A.. 1993; Generation and identification of recombinant adenovirus by liposome-mediated transfection and PCR analysis. Biotechniques15:868–872
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-10-2621
Loading
/content/journal/jgv/10.1099/0022-1317-80-10-2621
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error