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.

  • Article
  • Published:

Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations

Abstract

Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require neutralizing antibody and was active for a series of challenges ending with a highly virulent virus with a primary isolate envelope heterologous to the immunizing strain.

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: Vaccine trial.
Figure 2: Temporal antibody responses during the immunization and challenge phases of the vaccine trial.
Figure 3: Levels of viral RNA in plasma after the first, second and third challenges.
Figure 4: Titers of neutralizing antibody for the challenge virus on the days of the first, second and third challenges.

Similar content being viewed by others

References

  1. The World Health Organization in AIDS Epidemic Update (Joint United Nations Programme on HIV/AIDS and the World Health Organization, Geneva, 1998).

  2. Moore, J.P. & Ho, D.D. HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells. AIDS 9, S117–136 (1995).

    PubMed  Google Scholar 

  3. Burton, D.R. & Moore, J.P. Why do we not have an HIV vaccine and how can we make one? Nature Med. 4, 495–498 (1998).

    Article  CAS  Google Scholar 

  4. Rosenberg, E.S. et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447– 1450 (1997).

    Article  CAS  Google Scholar 

  5. Schacker, T.W., Hughes, J.P., Shea, T., Coombs, R.W. & Corey, L. Biological and virologic characteristics of primary HIV infection. Ann. Intern. Med. 128, 613 –620 (1998).

    Article  CAS  Google Scholar 

  6. Finzi, D. & Silliciano, R.F. Viral dynamics in HIV-1 infection. Cell 93, 665–671 (1998).

    Article  CAS  Google Scholar 

  7. Daniel, M.D., Kirchhoff, F., Czajak, S.C., Sehgal, P.K. & Desrosiers, R.C. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258, 1938–1941 ( 1992).

    Article  CAS  Google Scholar 

  8. Baba, T.W. et al. Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267, 1820– 1825 (1995).

    Article  CAS  Google Scholar 

  9. Ruprecht, R.M., Baba, T.W. & Liska, V. Attenuated HIV vaccine: caveats. Science 271, 1790–1792 (1996).

    Article  CAS  Google Scholar 

  10. Mascola, J.R. et al. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. J. Infect. Dis. 173, 340–348 ( 1996).

    Article  CAS  Google Scholar 

  11. Connor, R.I. et al. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J. Virol. 72, 1552 –1576 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Graham, B.S. et al. Analysis of intercurrent human immunodeficiency virus type 1 infections in phase I and II trials of candidate AIDS vaccines. AIDS Vaccine Evaluation Group, and the Correlates of HIV Immune Protection Group. J. Infect. Dis. 177, 310–319 (1998).

    Article  CAS  Google Scholar 

  13. Moss, B. Recombinant DNA virus vectors for vaccination. Semin. Immunol. 2, 317–327 ( 1990).

    CAS  PubMed  Google Scholar 

  14. Tartaglia, J. et al. Canarypox virus-based vaccines: prime-boost strategies to induce cell- mediated and humoral immunity against HIV. AIDS Res. Hum. Retroviruses 14 Suppl 3, S291– 298 (1998).

    Google Scholar 

  15. Stott, J. & Hu, S.L. AIDS 1998. Vaccines and immunology: overview. AIDS 12, S95– 96 (1998).

    Article  Google Scholar 

  16. Hu, S.-L. et al. in Transmembrane Protein and Core Antigens in Protection against SIV Infection (eds. Chanock, R.M., Brown, F., Ginsberg, H.S. & Norrby, E.) 167–173 (Cold Spring Harbor Laboratory Press, New York, 1995).

    Google Scholar 

  17. Robinson, H.L. & Torres, C.A. DNA vaccines. Semin. Immunol. 9, 271– 283 (1997).

    Article  CAS  Google Scholar 

  18. Donnelly, J.J., Ulmer, J.B., Shiver, J.W. & Liu, M.A. DNA vaccines. Annu. Rev. Immunol. 15, 617 –648 (1997).

    Article  CAS  Google Scholar 

  19. Boyer, J.D. et al. Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA vaccination. Nature Med. 3, 526–532 (1997).

    Article  CAS  Google Scholar 

  20. Letvin, N.L. et al. Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination. Proc. Natl. Acad. Sci. USA 94, 9378–9383 (1997).

    Article  CAS  Google Scholar 

  21. Li, J., Lord, C.I., Haseltine, W., Letvin, N.L. & Sodroski, J. Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. J. Acquir. Immune Defic. Syndr. 5, 639– 646 (1992).

    CAS  PubMed  Google Scholar 

  22. Li, J.T. et al. Persistent infection of macaques with simian-human immunodeficiency viruses. J. Virol. 69, 7061– 7067 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Reimann, K.A. et al. A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J. Virol. 70, 6922–6928 ( 1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Lu, S. et al. Simian immunodeficiency virus DNA vaccine trial in macaques. J. Virol. 70, 3978–3991 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Fynan, E.F. et al. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc. Natl. Acad. Sci. USA 90, 11478–11482 (1993).

    Article  CAS  Google Scholar 

  26. Pertmer, T.M. et al. Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13, 1427– 1430 (1995).

    Article  CAS  Google Scholar 

  27. Klaniecki, J. et al. Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus. AIDS Res. Hum. Retroviruses 7, 791– 798 (1991).

    Article  CAS  Google Scholar 

  28. Jenkins, S. et al. Formation of lentivirus particles by mammalian cells infected with recombinant fowlpox virus. AIDS Res. Hum. Retroviruses 7, 991–998 (1991).

    Article  CAS  Google Scholar 

  29. Johnson, R.P. et al. Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus. J. Virol. 71, 7711–8 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Richmond, J.F. et al. Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting. J. Virol. 72, 9092– 9100 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Suryanarayana, K., Wiltrout, T.A., Vasquez, G.M., Hirsch, V.M. & Lifson, J.D. Plasma SIV RNA viral load determination by real-time quantification of product generation in reverse transcriptase-polymerase chain reaction. AIDS Res. Hum. Retroviruses 14, 183–189 (1998).

    Article  CAS  Google Scholar 

  32. Wyand, M.S., Manson, K.H., Garcia-Moll, M., Montefiori, D. & Desrosiers, R.C. Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. J. Virol. 70, 3724–3733 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Montefiori, D.C. & Evans, T.G. Toward an HIV-type 1 vaccine that generates potent, broadly cross-reactive neutralizing antibodies. AIDS Res. and Hum. Retroviruses 15, 689 –698 (1999).

    Article  CAS  Google Scholar 

  34. Yang, O.O. et al. Lysis of HIV-1-infected cells and inhibition of viral replication by universal receptor T cells. Proc. Natl. Acad. Sci. USA 94, 11478–11483 (1997).

    Article  CAS  Google Scholar 

  35. Levy, J.A., Mackewicz, C.E. & Barker, E. Controlling HIV pathogenesis: the role of the noncytotoxic anti-HIV response of CD8+ T cells. Immunol. Today 17 , 217–224 (1996).

    Article  CAS  Google Scholar 

  36. Feltquate, D.M., Heaney, S., Webster, R.G. & Robinson, H.L. Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158, 2278–84 (1997).

    CAS  PubMed  Google Scholar 

  37. O'Garra, A. & Murphy, K. Role of cytokines in determining T-lymphocyte function. Curr. Opin. Immunol. 6, 458–66 (1994).

    Article  CAS  Google Scholar 

  38. Seder, R.A. & Paul, W.E. Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu. Rev. Immunol. 12, 635–673 (1994).

    Article  CAS  Google Scholar 

  39. Dittmer, U., Brooks, D.M. & Hasenkrug, K.J. Requirement for multiple lymphocyte subsets in protection by a live attenuated vaccine against retroviral infection. Nature Med. 5, 189–193 ( 1999).

    Article  CAS  Google Scholar 

  40. Johnson, R.P. Live attenuated AIDS vaccines: hazards and hopes. Nature Med 5, 154–155 (1999).

    Article  CAS  Google Scholar 

  41. Schneider, J. et al. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nature Med. 4, 397– 402 (1998).

    Article  CAS  Google Scholar 

  42. Sedegah, M. et al. Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine. Proc. Natl. Acad. Sci. USA 95, 7648–7653 ( 1998).

    Article  CAS  Google Scholar 

  43. Kent, S.J. et al. Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. J. Virol. 72, 10180–10188 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Polacino, P. et al. Limited breadth of the protective immunity elicited by simian immunodeficiency virus SIVmne gp160 vaccines in a combination immunization regimen. J. Virol. 73, 618– 630 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Gritz, L. et al. Generation of hybrid genes and proteins by vaccinia virus-mediated recombination: application to human immunodeficiency virus type 1 env. J. Virol. 64, 5948–5957 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Andersson, S., Davis, D.L., Dahlback, H., Jornvall, H. & Russell, D.W. Cloning, structure, and expression of the mitochondrial cytochrome P- 450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J. Biol. Chem. 264, 8222–8229 (1989).

    CAS  PubMed  Google Scholar 

  47. Earl, P.L. et al. Native oligomeric human immunodeficiency virus type 1 envelope glycoprotein elicits diverse monoclonal antibody reactivities. J. Virol. 68, 3015–3026 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Schochetman, G., Subbarao, S. & Kalish, M.L. in Viral Genome Methods (ed. K.W. Adolph) 25–41 (CRC Press, Boca Raton, 1996 ).

    Google Scholar 

  49. Montefiori, D.C., Robinson, W.E. Jr., Schuffman, S.S. & Mitchell, W.M. Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay. J. Clin. Microbiol. 26, 231– 235 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank M. Feinberg and J. Safrit for critical comments on the manuscript. We are indebted to H. Drake-Perrow for administrative assistance. We thank M. Piatak, L. Li, and T. Parks for assistance with SIV RNA viral load analysis; J. Yang for assistance with T-cell assays; R. Schmidt for help in construction of pRS102; and A. Saekhou for assistance with analyses of transferred virus. This research was supported by NIH grants R01-AI-34241 and P01-AI-43045 (H.L.R.); R01-AI-40334 (S.L.); P01-AI-26503 (S.-L.H.) R01 AI 52634, RR 000138 (R. P. Johnson) and U01 AI 26507 (D.L.P.); by the Yerkes Primate Research Center Base Grant, RR-00165; and by contracts NCI-6S-1649 (D.C.M.) and NO1-CO-56000 (J.D.L.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robinson, H., Montefiori, D., Johnson, R. et al. Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations . Nat Med 5, 526–534 (1999). https://doi.org/10.1038/8406

Download citation

  • Received:

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1038/8406

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing