Skip to main content

Prospects and Problems in Synthetic Vaccine Development: What did We Learn from the Cholera Toxin System?

  • Chapter
Immunobiology of Proteins and Peptides V
  • 110 Accesses

Abstract

The cholera toxin is a 84-kilodalton protein composed of two noncovalently bound subunits, A and B. The A subunit is the proenzyme form of an ADP-ribosyltransferase that is responsible for the biological activity of the toxin through its ability to activate target cell adenylate cyclase. The B subunit is the immunologically dominant region consisting of five identical, noncovalently associated B chains composed of 103 amino acids that are responsible for binding the toxin to target cell membrane receptors containing the oligosaccharide of the GM1 ganglioside. Neutralizing antibodies raised against the holotoxin react mainly with the B subunit, and antibodies against the B subunit are capable of neutralizing the biological activity of the intact toxin.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Audibert, F., Jolivet, M., Chedid, L., Arnon, R., and Sela, M. (1982), Successful immunization with a totally synthetic diphteria vaccine, Proc. Natl. Acad. Sci. U.S.A. 79:5042–5046.

    Article  PubMed  CAS  Google Scholar 

  • Bavoil, P., Newton, S., Stocker, B. A., D., and Jacob, C. O. (unpublished data).

    Google Scholar 

  • Charbit, A., Boulain, J. C., Ryter, A., and Hofnung, M. (1986), Probing the topology of a bacterial membrane protein by genetic insertion of a foreign epitope ; expression at the ell surface, EMBO J. 5:3029–3039.

    PubMed  CAS  Google Scholar 

  • DeWolf, M. J. S., Fridkin, M., Epstein, M., and Kohn, L. D. (1981), Structure-function studies of cholera toxin and its A and B promoters ; modification of tryptophan residues, J. Biol. Chem. 256:5481–5488.

    CAS  Google Scholar 

  • Duffy, L. K. and Lai, C. Y. (1979), Involvement of arginine residues in the binding site of cholera toxin subunit B, Biochem. Biophys. Res. Commun. 91:1005–1010.

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein, R. A., Burks, M. F., Zupan, A., Dallas, W. S., Jacob, C. O., and Ludwig, D. S. (1987), Antigenic determinants of the cholera/coli family of enterotoxins, Rev. Infect. Dis. 9:S490-S502.

    Article  Google Scholar 

  • Herzenberg, L. A., Tokuhira, T., and Herzenberg, L. H. (1980), Carrier-priming leads to hapten-specific suppression, Nature 285:664–667.

    Article  PubMed  CAS  Google Scholar 

  • Hopp, T. P. (1984), Immunogenicity of a synthetic HBsAg peptide:Enhancement by conjuation to a fatty acid carrier, Mol. Immunol. 21:13–16.

    Article  PubMed  CAS  Google Scholar 

  • Jacob, C. O., Harari, I., Arnon, R., and Sela, M. (1986), Antibodies to cholera toxin synthetic peptides of increasing size and their reactivity with related toxins, Vaccine 4:9–98.

    Article  Google Scholar 

  • Jacob, C. O., Pimes, M., and Arnon, R. (1984), Neutralization of heat-labile toxin of E. coli by antibodies to synthetic peptides derived from B subunit of cholera toxin, EMBO J. 3:2889–2893.

    PubMed  CAS  Google Scholar 

  • Jacob, C. O., Arnon, R., and Sela, M. (1985), Effect of carrier on the immunogenic capacity of synthetic cholera vaccine, Mol. Immunol. 22:1333–1339.

    Article  PubMed  CAS  Google Scholar 

  • Jacob, C. O., Arnon, R., and Sela, M. (1986), Anti-cholera response elicited in aqueous solution by a completely synthetic antigen with built- in adjuvanticity, Immunol. Letters 14:43–48.

    Article  CAS  Google Scholar 

  • Jacob, C. O., Sela, M., Pimes, M., Hurwitz, S., and Arnon, R. (1984), Both cholera toxin- induced adenylate cyclase activation and cholera toxin induced biological activity are inhibited by antibodies against related synthetic peptides, Proc. Natl. Acad. Sci. U. S.A. 81:7893–7896.

    Article  PubMed  CAS  Google Scholar 

  • Jacob, C. O., Leitner, M., Zamir, A., Salomon, D., and Arnon, R. (1985), Priming immunization against cholera toxin and E. coli heat-labile toxin by a cholera toxin short peptide- β-galactosidase hybrid synthesized in E. coli, EMBO J. 4:3339–3343.

    PubMed  CAS  Google Scholar 

  • Newton, S. M. C., Jacob, C. O., and Stocker, B. A. D. ( (1989), Immune response to cholera toxin epitope inserted in Salmonella flagellin, Science (in press).

    Google Scholar 

  • Sela, M., and Arnon, R.(1960), Studies on the chemical basis of the antigenicity of proteins. The role of rigidity in the antigenicity of polypeptidyl gelatins, Biochem. J. 77:394–399.

    PubMed  CAS  Google Scholar 

  • Shapira, M., personal communication.

    Google Scholar 

  • Siddiqui, W. A., Kan, S. C., Kramer, K., Case, S., Palmer, K. (1981), Use of a synthetic adjuvant in an effective vaccination of monkeys against malaria, Nature 289:64–66.

    Article  PubMed  CAS  Google Scholar 

  • Skehel, J. J., and Ada, G. L. (1985), Are peptides good antigens? Nature 316:764–765.

    Article  PubMed  Google Scholar 

  • Westhof, E., Altschuk, D., Moras, D., Bloomer, A. C., Mondragon, A., Klug, A., and Van Regenmortel, M. H. V. (1984), Correlation between segmental mobility and the location of antigenic determinants in proteins, Nature 311:123–126.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer Science+Business Media New York

About this chapter

Cite this chapter

Jacob, C.O. (1989). Prospects and Problems in Synthetic Vaccine Development: What did We Learn from the Cholera Toxin System?. In: Atassi, M.Z. (eds) Immunobiology of Proteins and Peptides V. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2046-4_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2046-4_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-2048-8

  • Online ISBN: 978-1-4757-2046-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics