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.

  • Research Article
  • Published:

Immunity to Plasmodium falciparum malaria sporozoites by somatic transgene immunization

Nature Biotechnology volume 15, pages 876–881 (1997)Cite this article

Abstract

Immunity against the human malaria parasite Plasmodium falciparum was induced using somatic transgene immunization, a method to effectively target B lymphocytes in vivo. A single inoculation of plasmid DNA containing an immunoglobulin heavy-chain gene coding in the complementarity-determining region 3 for three repeats of the sequence Asn-Ala-Asn-Pro (NANP), a B-cell epitope of P. falciparum sporozoites, induced antibodies against NANP in all mice. A booster with an antibody antigenized with the NANP peptide, or challenge with P. falciparum sporozoites, demonstrated the establishment of immunologic memory. Immunity to a parasite antigen can be induced by exploiting mechanisms in which B lymphocytes are both the source of the immunogen as well as the effector mechanism of immunity. The results indicate that somatic transgene immunization is a potential approach for vaccination against foreign pathogens.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Salk, J. and Salk, D. 1977. Control of influenza and poliomyelitis with killed virus vaccines. Science 195: 834–847.

    Article  CAS  PubMed  Google Scholar 

  2. Zanetti, M., Sercarz, E., and Salk, J. 1987. The immunology of new generation vaccines. Immunol. Today 8: 18–25.

    Article  CAS  PubMed  Google Scholar 

  3. Cox, G., Zamb, T., and Babiuk, L. 1993. Bovine herpesvirus1: Immune responses in mice and cattle injected with plasmid DNA. J. Virol. 67: 5664–5667.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Robinson, H., Hunt, L. and Webster, R. (1993). Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid. Vaccine 11: 957–960.

    Article  CAS  PubMed  Google Scholar 

  5. Wang, B., Ugen, K., Srikantan, V., Agadjanyan, M., Dang, Y., Refaeli, A. et al. 1993. Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 90: 4156–4160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ulmer, J.B., Donnelly, J.J., Parker, S.E., Rhodes, G.H. Felgner, R.L., Dwarki, V.J., et al. 1993. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745–1749.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Raz, E., Carson, D.A., Parker, S.E., Parr, T.B., Abai, A.M., Aichinger, G., et al. 1994. Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses. Proc. Natl. Acad. Sci. USA 91: 9519–9523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Davis, H.L., Michel, M.L., Mancini, M., Schleef, M., and Whalen, R.G. 1994. Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine 12: 1503–1509.

    Article  CAS  PubMed  Google Scholar 

  10. Anderson, R., Gao, X.-M., Papakonstantinopoulou, A., Roberts, M., and Dougan, G. 1996. Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin. Infect. Imm. 64: 3168–3173.

    CAS  Google Scholar 

  11. Xiang, Z.Q., Spitalnik, S., Iran, M., Wunner, W.H., Cheng, J., and Ertl, H.C. 1994. Vaccination with a plasmid vector carrying the rabies virus glycoprotein gene induces protective immunity against rabies virus. Virology 199: 132–140.

    Article  CAS  PubMed  Google Scholar 

  12. Davis, H.L., Whalen, R.G., and Demeneix, B.A. 1993. Direct gene transfer into skeletal muscle in vivo: factors affecting efficiency of transfer and stability of expression. Hum. Gene Ther. 4: 151–159.

    Article  PubMed  Google Scholar 

  13. Gerloni, M., Billetta, R., Xiong, S., and Zanetti, M. 1997. Somatic transgene immunization with DNA encoding an immunoglobulin heavy chain. DNA Cell Biol. 16: 611–625.

    Article  CAS  PubMed  Google Scholar 

  14. Gillies, S.D., Morrison, S.L., Oi, V.T., and Tonegawa, S. 1983. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33: 717–728.

    Article  CAS  PubMed  Google Scholar 

  15. Xiong, S., Gerloni, M., and Zanetti, M. 1997. in vivo role of B lymphocytes in somatic transgene immunization. Proc. Natl. Acad. Sci. USA 94: 6352–6357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zanetti, M. 1992. Antigenized antibodies. Nature 365: 466–477

    Google Scholar 

  17. Billetta, R., Hollingdale, R.M., and Zanetti, M. 1991. Immunogenicity of an engineered internal image antibody. Proc. Natl. Acad. Sci. USA 88: 4713–4717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lanza, P., Billetta, R., Antonenko, S., and Zanetti, M. 1993. Active immunity against the CD4 receptor using an antibody antigenized with residues 41–55 of the first extracellular domain. Proc. Natl. Acad. Sci. USA 90: 11683–11687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rigaudy, P., Simon, S., Hunter, T., Sollazzo, M., Billetta, R., Zanetti, M., and Eckhart, W. 1994. Antibodies specific for the neuronal form of the scr protein elicited by an antigenized antibody. DNA Cell Biol. 13: 585–591.

    Article  CAS  PubMed  Google Scholar 

  20. Zaghouani, H., Anderson, S.A., Sperber, K.E., Daian, C., Kennedy, R.C., Mayer, L., and Bona, C.A. 1995. Induction of antibodies to the human immunodeficiency virus type 1 by immunization of baboons with immunoglobulin molecules carrying the principal neutralizing determinant of the envelope protein. Proc. Natl. Acad. Sci. USA 92: 631–635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sollazzo, M., Billetta, R., and Zanetti, M. Expression of an exogenous peptide epitope genetically engineereed in the variable domain of an immunoglobulin: implications for antibody and peptide folding. Prot. Eng. 4: 215–220. 1990.

    Article  CAS  Google Scholar 

  22. Zaghouani, H., Steinman, R., Nonacs, R., Shah, H., Gerhard, W., and Bona, C. 1993. Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science 259: 224–227.

    Article  CAS  PubMed  Google Scholar 

  23. Zavala, F., Tam, J.P., Hollingdale, M.R., Cochrane, A.H., Quakyi, I., Nussenzweig, R.S., and Nussenzweig, V. 1985. Rationale for development of a synthetic vaccine against Plasmodium falciparum malaria. Science 228: 1436–1440.

    Article  CAS  PubMed  Google Scholar 

  24. Nardin, E.H., Nussenzweig, R.S., McGregor, I.A., and Bryan, J.H. 1979. Antibodies to sporozoites: Their frequent occurrence in individuals living in an area of hyperendemic malaria. Science 206: 597–601.

    Article  CAS  PubMed  Google Scholar 

  25. Clyde, D.F., McCarthy, V.C., Miller, R.M., and Hornick, R.B. 1973. Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am. J. Med. Sci. 266: 398–403.

    Article  CAS  PubMed  Google Scholar 

  26. Calle, J.M., Nardin, E.H., Clavijo, P., Boudin, C., Stuber, D., Takacs, B., et al. 1992. Recognition of different domains of the Plasmodium falciparum CS protein by the sera of naturally infected individuals compared with those of sporozoite-immunized volunteers. J. Immunol. 149: 2695–2701.

    CAS  PubMed  Google Scholar 

  27. Egan, J.E., Hoffman, S.L., Haynes, J.D., Sadoff, J.C., Schneider, I., Grau, G.E., et al. 1993. Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. Am. J. Trop. Med. Hyg. 49: 166–173.

    Article  CAS  PubMed  Google Scholar 

  28. Ballou, W.R., Hoffman, S.L., Sherwood, J.A., Hollingdale, M.R., Neva, F.A., Hockmeyer, W.T., et al. 1987. Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet 1: 1277–1281.

    Article  CAS  PubMed  Google Scholar 

  29. Herrington, D.A., Clyde, D.F., Losonsky, G., Cortesia, M., Murphy, J.R., Davis, J. et al. 1987. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature 328: 257–259.

    Article  CAS  PubMed  Google Scholar 

  30. Edelman, R., Hoffman, S.L., Davis, J.R., Beier, M., Sztein, M.B., Losonsky, G. et al. 1963. Long-term persistence of sterile immunity in a volunteer immunized with X-irradiated Plasmodium falciparum sporozoites. J. Infect Dis 168: 1066–1070.

    Article  Google Scholar 

  31. Dresser, D.W. and Mitchison, N.A. 1968. The mechanism of immunological paralysis. Adv. Immunol. 8: 129–181.

    Article  CAS  PubMed  Google Scholar 

  32. Stoute, J.A., Slaoui, M., Heppner, D.G., Momin, P., Kester, K.E., Desmons, P., et al. 1997. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS.S Malaria Vaccine Evaluation Group [see comments]. New Engl. J. Med. 336: 86–91.

    Article  CAS  PubMed  Google Scholar 

  33. Munesinghe, D.Y., Clavijo, P., Calle, M.C., Nussenzweig, R.S., and Nardin, E. 1991. Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein. Eur. J. Immunol. 21: 3015–3020.

    Article  CAS  PubMed  Google Scholar 

  34. Xiong, S., Gerloni, M., and Zanetti, M. 1997. Engineering vaccines with heterologous B and T cell epitopes using immunoglobulin genes. Nature Biotechnology 15: 882–886.

    Article  CAS  PubMed  Google Scholar 

  35. Gerloni, M., Lo, D., and Zanetti, M. 1997. DNA immunization in relB-deficient mice discloses a role for dendritic cells in IgG1-IgM switch in vivo. Eur. J. Immunol. Eur. J. Immunol. In press.

  36. Kemp, D.J., Coppel, R.L., and Anders, R.F. 1987. Repetitive proteins and genes of malaria. Annu. Rev. Microbiol. 41: 181–208.

    Article  CAS  PubMed  Google Scholar 

  37. Hoffman, S.L., Nussenzweig, V., Sadoff, J.C., and Nussenzweig, R.S. 1991. Progress toward malaria vaccine preerythrocytic vaccines. Science 252: 520–521.

    Article  CAS  PubMed  Google Scholar 

  38. Etlinger, H.M. and Trzeciak, A. 1993. Towards a synthetic malaria vaccine: cyclization of a peptide eliminates the production of parasite-unreactive antibody. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 340: 69–72.

    Article  CAS  PubMed  Google Scholar 

  39. Green, T.J. and Packer, B.J. 1984. A role for rheumatoid factor enhancement of Plasmodium falciparum schizont inhibition in vitro. Infect. Immun. 46: 668–672.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Wirtz, R.A., Ballou, W.R., Schneider, I., Chedid, L., Gross, M.J., Young, J.F. et al. 1987. Plasmodium falciparum: immunogenicity of circumsporozoite protein constructs produced in Escherichia coli. Exp. Parasitol. 63: 166–172.

    Article  CAS  PubMed  Google Scholar 

  41. Billetta, R. and Zanetti, M. 1992. Ligand expression using antigenization of antibody: Principle and methods. ImmunoMeihods 1: 41–51.

    Article  CAS  Google Scholar 

  42. Sollazzo, M., Hasemann, C.A., Meek, K.D., Glotz, D., Capra, J.D., and Zanetti, M. 1989. Molecular characterization of the VH region of murine autoan-tibodies from neonatal and adult BALB/c mice. Eur. J. Immunol. 19: 453–457.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Department of Medicine and Cancer Center, University of California, San Diego, 9500 Oilman Dr., La Jolla, CA, 92093-0063

    Mara Gerloni, Rosario Billetta & Maurizio Zanetti

  2. Department of Immunology, Walter Reed Army Institute for Research, Rockville, MD

    W. Ripley Ballou

Authors
  1. Mara Gerloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Ripley Ballou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rosario Billetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maurizio Zanetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maurizio Zanetti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerloni, M., Ballou, W., Billetta, R. et al. Immunity to Plasmodium falciparum malaria sporozoites by somatic transgene immunization. Nat Biotechnol 15, 876–881 (1997). https://doi.org/10.1038/nbt0997-876

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0997-876

This article is cited by

Search

Advanced 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