Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 Jul 1;164(1):227–236. doi: 10.1084/jem.164.1.227

A surrogate hepatitis B virus antigenic epitope represented by a synthetic peptide and an internal image antiidiotype antibody

PMCID: PMC2188204  PMID: 2425029

Abstract

The use of molecules that represent single, defined epitopes able to substitute for antigen (i.e. surrogate antigens) offers considerable advantages over the use of native antigen for the precise manipulation of the immune response. We have investigated the immunochemical characteristics of two types of surrogate hepatitis B surface antigen (HBsAg) epitopes: (a) linear and cyclical synthetic peptides representing amino acid residues 139-147, a hydrophilic region corresponding to part of the a determinant of the HBsAg, and (b) four monoclonal antiidiotypes raised against anti-HBs mAb, two of which behave as an internal image of an a determinant. Polyclonal anti-HBs antisera bound the monoclonal antiidiotypes with affinities of the order of 10(8)/M, and to the peptides with greater than 10-fold lower affinities. However, the levels of antibody in the polyclonal antisera for the peptides was greater than for the antiidiotypes. In inhibition RIA, the surrogate antigens show concordance in that the internal image antiidiotypes inhibit the binding of both monoclonal and polyclonal anti-HBs to the linear and cyclical 139-147 peptides. These results imply that surrogate antigens could indeed be useful as potential hepatitis vaccines, but while the antiidiotypes may stimulate B cells of higher affinity, they would react with a more restricted range of B cell reactivities than would the peptides. A future HBV vaccine may thus comprise a synthetic peptide such as cyclical 139-147 or a cluster of monoclonal internal image antiidiotypes.

Full Text

The Full Text of this article is available as a PDF (550.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon R., Shapira M., Jacob C. O. Synthetic vaccines. J Immunol Methods. 1983 Jul 29;61(3):261–273. doi: 10.1016/0022-1759(83)90220-x. [DOI] [PubMed] [Google Scholar]
  2. Bona C. A., Victor-Kobrin C., Manheimer A. J., Bellon B., Rubinstein L. J. Regulatory arms of the immune network. Immunol Rev. 1984 Jun;79:25–44. doi: 10.1111/j.1600-065x.1984.tb00485.x. [DOI] [PubMed] [Google Scholar]
  3. Brown S. E., Howard C. R., Zuckerman A. J., Steward M. W. Affinity of antibody responses in man to hepatitis B vaccine determined with synthetic peptides. Lancet. 1984 Jul 28;2(8396):184–187. doi: 10.1016/s0140-6736(84)90479-3. [DOI] [PubMed] [Google Scholar]
  4. Brown S. E., Howard C. R., Zuckerman A. J., Steward M. W. Determination of the affinity of antibodies to hepatitis B surface antigen in human sera. J Immunol Methods. 1984 Aug 3;72(1):41–48. doi: 10.1016/0022-1759(84)90431-9. [DOI] [PubMed] [Google Scholar]
  5. Ertl H. C., Homans E., Tournas S., Finberg R. W. Sendai virus-specific T cell clones. V. Induction of a virus-specific response by antiidiotypic antibodies directed against a T helper cell clone. J Exp Med. 1984 Jun 1;159(6):1778–1783. doi: 10.1084/jem.159.6.1778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gaze S., West N. J., Steward M. W. The use of a double isotope method in the determination of antibody affinity. J Immunol Methods. 1973 Dec;3(4):357–364. doi: 10.1016/0022-1759(73)90037-9. [DOI] [PubMed] [Google Scholar]
  7. Hilleman M. R., McAleer W. J., Buynak E. B., McLean A. A. Quality and safety of human hepatitis B vaccine. Dev Biol Stand. 1983;54:3–12. [PubMed] [Google Scholar]
  8. Kennedy R. C., Dreesman G. R. Enhancement of the immune response to hepatitis B surface antigen. In vivo administration of antiidiotype induces anti-HBs that expresses a similar idiotype. J Exp Med. 1984 Mar 1;159(3):655–665. doi: 10.1084/jem.159.3.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Liew F. Y. New aspects of vaccine development. Clin Exp Immunol. 1985 Nov;62(2):225–241. [PMC free article] [PubMed] [Google Scholar]
  10. McAleer W. J., Buynak E. B., Maigetter R. Z., Wampler D. E., Miller W. J., Hilleman M. R. Human hepatitis B vaccine from recombinant yeast. Nature. 1984 Jan 12;307(5947):178–180. doi: 10.1038/307178a0. [DOI] [PubMed] [Google Scholar]
  11. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  12. McNamara M. K., Ward R. E., Kohler H. Monoclonal idiotope vaccine against Streptococcus pneumoniae infection. Science. 1984 Dec 14;226(4680):1325–1326. doi: 10.1126/science.6505692. [DOI] [PubMed] [Google Scholar]
  13. Roitt I. M., Cooke A., Male D. K., Hay F. C., Guarnotta G., Lydyard P. M., de Carvalho L. P., Thanavala Y., Ivanyi J. Idiotypic networks and their possible exploitation for manipulation of the immune response. Lancet. 1981 May 9;1(8228):1041–1045. doi: 10.1016/s0140-6736(81)92199-1. [DOI] [PubMed] [Google Scholar]
  14. Sharpe A. H., Gaulton G. N., McDade K. K., Fields B. N., Greene M. I. Syngeneic monoclonal antiidiotype can induce cellular immunity to reovirus. J Exp Med. 1984 Oct 1;160(4):1195–1205. doi: 10.1084/jem.160.4.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Shinnick T. M., Sutcliffe J. G., Green N., Lerner R. A. Synthetic peptide immunogens as vaccines. Annu Rev Microbiol. 1983;37:425–446. doi: 10.1146/annurev.mi.37.100183.002233. [DOI] [PubMed] [Google Scholar]
  16. Skelly J., Howard C. R., Zuckerman A. J. Analysis of hepatitis B surface antigen components solubilized with Triton X-100. J Gen Virol. 1979 Sep;44(3):679–689. doi: 10.1099/0022-1317-44-3-679. [DOI] [PubMed] [Google Scholar]
  17. Stein K. E., Söderström T. Neonatal administration of idiotype or antiidiotype primes for protection against Escherichia coli K13 infection in mice. J Exp Med. 1984 Oct 1;160(4):1001–1011. doi: 10.1084/jem.160.4.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Steward M. W., Howard C. R. The potential of synthetic peptides for vaccines. Med Lab Sci. 1985 Oct;42(4):376–387. [PubMed] [Google Scholar]
  19. Szmuness W., Stevens C. E., Harley E. J., Zang E. A., Alter H. J., Taylor P. E., DeVera A., Chen G. T., Kellner A. Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection. N Engl J Med. 1982 Dec 9;307(24):1481–1486. doi: 10.1056/NEJM198212093072403. [DOI] [PubMed] [Google Scholar]
  20. Tedder R. S., Guarascio P., Yao J. L., Lord R. B., Eddleston A. L. Production of monoclonal antibodies to hepatitis B surface and core antigens, and use in the detection of viral antigens in liver biopsies. J Hyg (Lond) 1983 Feb;90(1):135–142. doi: 10.1017/s0022172400063932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Thanavala Y. M., Bond A., Tedder R., Hay F. C., Roitt I. M. Monoclonal 'internal image' anti-idiotypic antibodies of hepatitis B surface antigen. Immunology. 1985 Jun;55(2):197–204. [PMC free article] [PubMed] [Google Scholar]
  22. Uytdehaag F. G., Osterhaus A. D. Induction of neutralizing antibody in mice against poliovirus type II with monoclonal anti-idiotypic antibody. J Immunol. 1985 Feb;134(2):1225–1229. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES