Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Chimpanzee-origin adenovirus vectors as vaccine carriers

Abstract

Vaccines based on replication-defective adenoviral vectors are being developed for infectious agents and tumor-associated antigens. Early work focused on vaccines derived from a common human serotype of adenovirus, that is, adenovirus of the serotype 5 (AdHu5). Neutralizing antibodies against AdHu5 virus, present in a large percentage of the human population, dampen the efficacy of vaccines based on this carrier. To circumvent this problem, we generated vectors derived from chimpanzee adenoviruses. Here we describe some basic parameters of vectors derived from chimpanzee adenoviruses C68 and C7, including growth characteristics, yields of infectious particles, effects of additional deletions in E3 and E4 and lengths of the inserted foreign sequence as they relate to the suitability for their eventual development as vaccine carriers for clinical use.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Wilson JM . Adenoviruses as gene-delivery vehicles. N Engl J Med 1996; 334: 1185–1187.

    Article  CAS  PubMed  Google Scholar 

  2. Shiver JW, Emini EA . Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med 2004; 55: 355–372.

    Article  CAS  PubMed  Google Scholar 

  3. Tatsis N, Ertl HC . Adenoviruses as vaccine vectors. Mol Ther 2004; 10: 616–629.

    Article  CAS  PubMed  Google Scholar 

  4. Barouch DH, Nabel GJ . Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther 2005; 16: 149–156.

    Article  CAS  PubMed  Google Scholar 

  5. Lasaro MO, Ertl HC . Human Papillomavirus-associated cervical cancer: prophyllactic and therapeutic vaccines. Gene Ther Mol Biol 2004; 8: 291–306.

    Google Scholar 

  6. Fitzgerald JC, Gao GP, Reyes-Sandoval A, Pavlakis GN, Xiang ZQ, Wlazlo AP et al. A simian replication-defective adenoviral recombinant vaccine to HIV-1 gag. J Immunol 2003; 170: 1416–1422.

    Article  CAS  PubMed  Google Scholar 

  7. Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK et al. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 2002; 415: 331–335.

    Article  CAS  PubMed  Google Scholar 

  8. Xiang ZQ, Gao GP, Reyes-Sandoval A, Li Y, Wilson JM, Ertl HC . Oral vaccination of mice with adenoviral vectors is not impaired by preexisting immunity to the vaccine carrier. J Virol 2003; 77: 10780–10789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Prevec L, Campbell JB, Christie BS, Belbeck L, Graham FL . A recombinant human adenovirus vaccine against rabies. J Infect Dis 1990; 161: 27–30.

    Article  CAS  PubMed  Google Scholar 

  10. Patterson LJ, Malkevitch N, Venzon D, Pinczewski J, Gomez-Roman VR, Wang L et al. Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by using replicating adenovirus-SIV multigene vaccine priming and subunit boosting. J Virol 2004; 78: 2212–2221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xiang ZQ, Yang Y, Wilson JM, Ertl HC . A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier. Virology 1996; 219: 220–227.

    Article  CAS  PubMed  Google Scholar 

  12. Tims T, Briggs DJ, Davis RD, Moore SM, Xiang Z, Ertl HC et al. Adult dogs receiving a rabies booster dose with a recombinant adenovirus expressing rabies virus glycoprotein develop high titers of neutralizing antibodies. Vaccine 2000; 18: 2804–2807.

    Article  CAS  PubMed  Google Scholar 

  13. Fischer L, Tronel JP, Pardo-David C, Tanner P, Colombet G, Minke J et al. Vaccination of puppies born to immune dams with a canine adenovirus-based vaccine protects against a canine distemper virus challenge. Vaccine 2002; 20: 3485–3497.

    Article  CAS  PubMed  Google Scholar 

  14. Shiver JW . Development of an HIV-1 Vaccine based on a replication defective adenovirus vectors. Keystone Symposium; Banff, Alberta, Canada, 2005.

  15. Farina SF, Gao GP, Xiang ZQ, Rux JJ, Burnett RM, Alvira MR et al. Replication-defective vector based on a chimpanzee adenovirus. J Virol 2001; 75: 11603–11613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xiang Z, Gao G, Reyes-Sandoval A, Cohen CJ, Li Y, Bergelson JM et al. Novel, chimpanzee serotype 68-based adenoviral vaccine carrier for induction of antibodies to a transgene product. J Virol 2002; 76: 2667–2675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Reyes-Sandoval A, Fitzgerald JC, Grant R, Roy S, Xiang ZQ, Li Y et al. Human immunodeficiency virus type 1-specific immune responses in primates upon sequential immunization with adenoviral vaccine carriers of human and simian serotypes. J Virol 2004; 78: 7392–7399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Roy S, Gao G, Lu Y, Zhou X, Lock M, Calcedo R et al. Characterization of a family of chimpanzee adenoviruses and development of molecular clones for gene transfer vectors. Hum Gene Ther 2004; 15: 519–530.

    Article  CAS  PubMed  Google Scholar 

  19. Cohen CJ, Xiang ZQ, Gao GP, Ertl HC, Wilson JM, Bergelson JM . Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor. J Gen Virol 2002; 83: 151–155.

    Article  CAS  PubMed  Google Scholar 

  20. Windheim M, Hilgendorf A, Burgert HG . Immune evasion by adenovirus E3 proteins: exploitation of intracellular trafficking pathways. Curr Top Microbiol Immunol 2004; 273: 29–85.

    CAS  PubMed  Google Scholar 

  21. Yeh P, Dedieu JF, Orsini C, Vigne E, Denefle P, Perricaudet M . Efficient dual transcomplementation of adenovirus E1 and E4 regions from a 293-derived cell line expressing a minimal E4 functional unit. J Virol 1996; 70: 559–565.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Graham FL, Smiley J, Russell WC, Nairn R . Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 1977; 36: 59–74.

    Article  CAS  PubMed  Google Scholar 

  23. Fallaux FJ, Bout A, van der Velde I, van den Wollenberg DJ, Hehir KM, Keegan J et al. New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 1998; 9: 1909–1917.

    Article  CAS  PubMed  Google Scholar 

  24. Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN . Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol 1997; 71: 4892–4903.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Branton PE . Adenoviruses: Basic Biology to Gene Therapy. Landes Bioscience: Georgetown, 1999.

    Google Scholar 

  26. McMichael AJ, Hanke T . HIV vaccines 1983–2003. Nat Med 2003; 9: 874–880.

    Article  CAS  PubMed  Google Scholar 

  27. Burton DR . Antibodies, viruses and vaccines. Nat Rev Immunol 2002; 2: 706–713.

    Article  CAS  PubMed  Google Scholar 

  28. Lubeck MD, Natuk R, Myagkikh M, Kalyan N, Aldrich K, Sinangil F et al. Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by immunization. Nat Med 1997; 3: 651–658.

    Article  CAS  PubMed  Google Scholar 

  29. Pinto AR, Fitzgerald JC, Giles-Davis W, Gao GP, Wilson JM, Ertl HC . Induction of CD8+ T cells to an HIV-1 antigen through a prime boost regimen with heterologous E1-deleted adenoviral vaccine carriers. J Immunol 2003; 171: 6774–6779.

    Article  CAS  PubMed  Google Scholar 

  30. Casimiro DR, Tang A, Chen L, Fu TM, Evans RK, Davies ME et al. Vaccine-induced immunity in baboons by using DNA and replication-incompetent adenovirus type 5 vectors expressing a human immunodeficiency virus type 1 gag gene. J Virol 2003; 77: 7663–7668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Amara RR, Sharma S, Patel M, Smith JM, Chennareddi L, Herndon JG et al. Studies on the cross-clade and cross-species conservation of HIV-1 Gag-specific CD8 and CD4 T cell responses elicited by a clade B DNA/MVA vaccine in macaques. Virology 2005; 334: 124–133.

    Article  CAS  PubMed  Google Scholar 

  32. Xin KQ, Urabe M, Yang J, Nomiyama K, Mizukami H, Hamajima K et al. A novel recombinant adeno-associated virus vaccine induces a long-term humoral immune response to human immunodeficiency virus. Hum Gene Ther 2001; 12: 1047–1061.

    Article  CAS  PubMed  Google Scholar 

  33. Ramsburg E, Rose NF, Marx PA, Mefford M, Nixon DF, Moretto WJ et al. Highly effective control of an AIDS virus challenge in macaques by using vesicular stomatitis virus and modified vaccinia virus Ankara vaccine vectors in a single-boost protocol. J Virol 2004; 78: 3930–3940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ji L, Bouvet M, Price RE, Roth JA, Fang B . Reduced toxicity, attenuated immunogenicity and efficient mediation of human p53 gene expression in vivo by an adenovirus vector with deleted E1–E3 and inactivated E4 by GAL4-TATA promoter replacement. Gene Therapy 1999; 6: 393–402.

    Article  CAS  PubMed  Google Scholar 

  35. Rafii S, Dias S, Meeus S, Hattori K, Ramachandran R, Feuerback F et al. Infection of endothelium with E1(−)E4(+), but not E1(−)E4(−), adenovirus gene transfer vectors enhances leukocyte adhesion and migration by modulation of ICAM-1, VCAM-1, CD34, and chemokine expression. Circ Res 2001; 88: 903–910.

    Article  CAS  PubMed  Google Scholar 

  36. Grave L, Dreyer D, Dieterle A, Leroy P, Michou AI, Doderer C et al. Differential influence of the E4 adenoviral genes on viral and cellular promoters. J Gene Med 2000; 2: 433–443.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Support for this work was provided by funds from the NIH grant, 5P01AI052271-03. We thank the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health and Christina Cole for manuscript preparation

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H C J Ertl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tatsis, N., Tesema, L., Robinson, E. et al. Chimpanzee-origin adenovirus vectors as vaccine carriers. Gene Ther 13, 421–429 (2006). https://doi.org/10.1038/sj.gt.3302675

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302675

Keywords

This article is cited by

Search

Quick links