Notice: file_put_contents(): Write of 379795 bytes failed with errno=28 No space left on device in /opt/frankenphp/design.onmedianet.com/app/src/Arsae/CacheManager.php on line 36

Warning: http_response_code(): Cannot set response code - headers already sent (output started at /opt/frankenphp/design.onmedianet.com/app/src/Arsae/CacheManager.php:36) in /opt/frankenphp/design.onmedianet.com/app/src/Models/Response.php on line 17

Warning: Cannot modify header information - headers already sent by (output started at /opt/frankenphp/design.onmedianet.com/app/src/Arsae/CacheManager.php:36) in /opt/frankenphp/design.onmedianet.com/app/src/Models/Response.php on line 20
Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara | Nature Medicine
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:

Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara

Abstract

Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-γ-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.

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

Similar content being viewed by others

References

  1. Nussenzweig, V. & Nussenzweig, R.S. Rationale for the development of an engineered sporozoite malaria vaccine. Adv. Immunol. 45, 283–334 (1989).

    Article  CAS  PubMed  Google Scholar 

  2. Hill, A.V.S. et al Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360, 434–439 (1992).

    Article  CAS  PubMed  Google Scholar 

  3. Aidoo, M. et al Identification of conserved antigenic components for a cytotoxic T lymphocyte-inducing vaccine against malaria. Lancet 345, 1003–1007 (1995).

    Article  CAS  PubMed  Google Scholar 

  4. Rodrigues, M.M. CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria. Int. Immunol. 3, 579–585 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. Romero, P. et al Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature 341, 323–326 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. White, K.L., Snyder, H.L. & Krzych, U. MHC class l-dependent presentation of exoety-throcytic antigens to CD8+ T lymphocytes is required for protective immunity against Plasmodium berghei. J. Immunol. 156, 3374–3381 (1996).

    CAS  PubMed  Google Scholar 

  7. Doolan, D.L. et al Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity. J. Exp. Med. 183,1739–1746 (1996).

    Article  Google Scholar 

  8. Sedegah, M., Hedstrom, R., Hobart, P. & Hoffman, S.L. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc. Natl. Acad. Sci. USA 91, 9866–9870 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Doolan, D.L. & Hoffmann, S.L. Multi-gene vaccination against malaria: A multistage, multi-immune response approach. Parasitol. Today 13, 171–178 (1997).

    Article  Google Scholar 

  10. Bennink, J.R. et al. Recombinant vaccinia virus primes and stimulates influenza haemag-glutinin-specific cytotoxic T cells. Nature 311, 578–579 (1984).

    Article  CAS  PubMed  Google Scholar 

  11. Bender, B.S. et al. Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza. J. Virol. 70, 6418–6424 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Thomson, S.A. et al. Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T cell epitopes. J. Immunol. 157, 822–826 (1996).

    CAS  PubMed  Google Scholar 

  13. An, L.L., Pamer, E. & Whitton, J.L. A recombinant minigene vaccine containing a norv americ cytotoxic-T-lymphocyte epitope confers limited protection against Listeria mono-cytogenes infection. Infect. Immun. 64, 1685–1693 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Satchidanandam, V., Zavala, F. & Moss, B. Studies using a recombinant vaccinia virus expressing the circumsporozoite protein of Plasmodium berghei. Mol. Biochem. Parasitol. 48, 89–99 (1991).

    Article  CAS  PubMed  Google Scholar 

  15. Sedegah, M. et al. Active and passive immunization against Plasmodium yoelii sporozoites. Bull. World Health Organ. 68, 1009–1014 (1990).

    Google Scholar 

  16. Stickl, H., & Hochstein-Mintzel, V. Intracutaneous smallpox vaccination with a weak pathogenic vaccinia virus (“MVA virus”). Munch. Med/Wochenschr. 113, 1149–1153(1971).

    CAS  Google Scholar 

  17. Mayr, A. et al. The smallpox vaccination strain MVA: marker, genetic structure, experience gained with the parenteral vaccination and behavior in organisms with a debilitated defence mechanism. Zentralbl. Bakteriol. 167, 375–390 (1978).

    CAS  Google Scholar 

  18. Sutter, G. & Moss, B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc. Natl. Acad. Sci. USA 89, 10847–10851 (1992).

    Article  CAS  Google Scholar 

  19. Sutter, G. et al. A recombinant vector derived from the host range-restricted and highly attenuated MVA strain of vaccinia virus stimulates protective immunity in mice to influenza virus. Vaccine 12, 1032–1040 (1994).

    Article  CAS  PubMed  Google Scholar 

  20. Symons, J.A., Alcamí, A. & Smith, G.L. Vaccinia virus encodes a soluble type I interferon receptor of novel structure and broad species specificity. Cell 81, 551–560 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Alcamí, A. & Smith, G.L. A soluble receptor for interleukin-1β encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell 71, 153–167 (1992).

    Article  PubMed  Google Scholar 

  22. Lockyer, M.J., Davies, C.S., Suhrbier, A. & Sinden, R.E. Nucleotide sequence of the Plasmodium berghei circumsporozoite protein gene from the ANKA clone 2.34L. Nucleic Acid Res. 18, 376(1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Robson, K.J.H. et al. 84, 1–12 (1997).

  24. jaffe, R.I., Lowell, C.H. & Gordon, D.M. Differences in susceptibility among mouse strains to infection with Plasmodium berghei (ANKA clone) sporozoites and its relationship to protection by gamma-irradiated sporozoites. Am. J. Trop. Med. Hyg. 42, 309–313 (1990).

    Article  CAS  PubMed  Google Scholar 

  25. Seguin, M.C. et al. Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells. J. Exp. Med. 180, 353–358 (1994).

    Article  CAS  PubMed  Google Scholar 

  26. Renggli, J. et al. Elimination of P. berghei liver stages is independent of Fas (CD95/Apo-I) or perforin-mediated cytotoxicity. Parasite Immunol. 19, 145–148 (1997).

    Article  CAS  PubMed  Google Scholar 

  27. Weiss, W.R. et al. Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J. Exp. Med. 171, 763–773 (1990).

    Article  CAS  PubMed  Google Scholar 

  28. Li, S. et al. Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. Proc. Natl. Acad. Sci. USA 90, 5214–5218 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Moss, B. et al. Host range restricted, non-replicating vaccinia vims vectors as vaccine candidates. Adv. Exp. Med. Biol. 397, 7–13 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lanar, D.E. et al. Attenuated vaccinia virus-circumsporozoite protein recombinants confer protection against rodent malaria. Infect. Immun. 64, 1666–1671 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Alcamí, A. & Smith, G.L., Vacinia, cowpox and camelpox viruses encode soulble interferon-v receptors with a novel broad species specificity. J. Virol. 69, 4633–4639 (1995).

    PubMed  PubMed Central  Google Scholar 

  32. Plebanski, M., Elson, C.J. & Billington Dependency on interleukin-1 of primary human in vitro T cell responses to soluble antigens. Eur. J. Immunol. 22, 2353–2358 (1992).

    Article  CAS  PubMed  Google Scholar 

  33. Though, D.F., Borrow, P. & Sprent, J. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947–1950 (1996).

    Article  Google Scholar 

  34. Khusmith, S. et al. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science 252, 715–718 (1991).

    Article  CAS  PubMed  Google Scholar 

  35. Plebanski, M., Aidoo, M., Whittle, H.C. & Hill, A.V.S. Precursor frequency analysis of cytotoxic T lymphocytes to pre-erythrocytic antigens of Plasmodium falciparum in West Africa. J. Immunol. 158, 2849–2855 (1997).

    CAS  PubMed  Google Scholar 

  36. Hanke, T., Szawlowski, P. & Randall, R.E. Contruction of solid matrix-antibody-antigen complexes containing SIV p27 using tag-specific monoclonal antibody and tag-linked antigen. J. Gen. Virol. 73, 653–660 (1992).

    Article  Google Scholar 

  37. Mackett, M., Smith, G.L. & Moss, B. General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J. Virol. 49, 857–864 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Carroll, M.W. & Moss, B.E. E. coli beta-glucuronidase (GUS) as a marker for recombinant vaccinia viruses. Biotechniques 19, 352–356 (1995).

    CAS  PubMed  Google Scholar 

  39. Bodmer, H.C., Pemberton, R.M., Rothbard, J.B. & Askonas, B.A. Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein. Cell 52, 253–258(1988).

    Article  CAS  PubMed  Google Scholar 

  40. Gavin, M.A. et al. 151, 3971–3980 (1993).

  41. Davis, H.L. et al. Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine 12, 1503–1509 (1994).

    Article  CAS  PubMed  Google Scholar 

  42. Rodrigues, M. et al. Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity. J. Immunol. 153, 4636–4648 (1994).

    CAS  PubMed  Google Scholar 

  43. Brunner, K.T., Mauel, J., Cerottini, J.C. & Chapuis, B. Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology 14, 181–196 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schneider, J., Gilbert, S., Blanchard, T. et al. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nat Med 4, 397–402 (1998). https://doi.org/10.1038/nm0498-397

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nm0498-397

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