Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Apr;80(8):2365–2369. doi: 10.1073/pnas.80.8.2365

Chemically synthesized peptides of hepatitis B surface antigen duplicate the d/y specificities and induce subtype-specific antibodies in chimpanzees.

J L Gerin, H Alexander, J W Shih, R H Purcell, G Dapolito, R Engle, N Green, J G Sutcliffe, T M Shinnick, R A Lerner
PMCID: PMC393821  PMID: 6188163

Abstract

Synthetic peptides, predicted from the nucleotide sequence of the S gene of hepatitis B virus were analyzed in terms of the established specificities of the hepatitis B surface antigen. The analysis indicated that the group-specific alpha antigen is composed of at least three nonoverlapping sequences and that a relatively hydrophilic region of the surface antigen protein, spanning amino acid residues 110-137, specifies the major d and y subtype system. The d/y subtype appears to depend on changes in one or more variable amino acids at positions 127, 131, and 134 of the hepatitis B surface antigen protein. Peptide 49 (consisting of amino acid sequences of the y subtype for the region 110-137), coupled to a carrier protein and mixed with an adjuvant, stimulated a brisk anti-y response in chimpanzees, the relevant model of human response to hepatitis B virus immunization and infection. Experimental challenge with homologous hepatitis B virus resulted in a pattern of partial protection. The results offer promise for the application of chemically synthesized peptides as vaccines in the prophylaxis of hepatitis B virus disease.

Full text

PDF
2365

Selected References

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

  1. Atassi M. Z. Antigenic structure of myoglobin: the complete immunochemical anatomy of a protein and conclusions relating to antigenic structures of proteins. Immunochemistry. 1975 May;12(5):423–438. doi: 10.1016/0019-2791(75)90010-5. [DOI] [PubMed] [Google Scholar]
  2. Benjamini E., Michaeli D., Young J. D. Antigenic determinants of proteins of defined sequences. Curr Top Microbiol Immunol. 1972;58:85–134. doi: 10.1007/978-3-642-65357-5_3. [DOI] [PubMed] [Google Scholar]
  3. Bhatnagar P. K., Papas E., Blum H. E., Milich D. R., Nitecki D., Karels M. J., Vyas G. N. Immune response to synthetic peptide analogues of hepatitis B surface antigen specific for the a determinant. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4400–4404. doi: 10.1073/pnas.79.14.4400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bittle J. L., Houghten R. A., Alexander H., Shinnick T. M., Sutcliffe J. G., Lerner R. A., Rowlands D. J., Brown F. Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature. 1982 Jul 1;298(5869):30–33. doi: 10.1038/298030a0. [DOI] [PubMed] [Google Scholar]
  5. Dreesman G. R., Sanchez Y., Ionescu-Matiu I., Sparrow J. T., Six H. R., Peterson D. L., Hollinger F. B., Melnick J. L. Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptides. Nature. 1982 Jan 14;295(5845):158–160. doi: 10.1038/295158a0. [DOI] [PubMed] [Google Scholar]
  6. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
  7. Gerin J. L., Faust R. M., Holland P. V. Biophysical characterization of the adr subtype of hepatitis B antigen and preparation of anti-r sera in rabbits. J Immunol. 1975 Jul;115(1):100–105. [PubMed] [Google Scholar]
  8. Gold J. W., Shih J. W., Purcell R. H., Gerin J. L. Characterization of antibodies to the structural polypeptides of HGSAg: evidence for subtype-specific determinants. J Immunol. 1976 Oct;117(4):1404–1406. [PubMed] [Google Scholar]
  9. Green N., Alexander H., Olson A., Alexander S., Shinnick T. M., Sutcliffe J. G., Lerner R. A. Immunogenic structure of the influenza virus hemagglutinin. Cell. 1982 Mar;28(3):477–487. doi: 10.1016/0092-8674(82)90202-1. [DOI] [PubMed] [Google Scholar]
  10. Hess G., Shih J. W., Kaplan P. M., Gerin J. L. The demonstration of subtype (D or Y)-specific determinants on the surface of the presumed hepatitis B virus. J Immunol. 1977 Oct;119(4):1542–1544. [PubMed] [Google Scholar]
  11. Holland P. V., Purcell R. H., Smith H., Alter H. J. Subtyping of hepatitis-associated antigen (HB-Ag); simplified technique with counterelectrophoresis. J Immunol. 1972 Sep;109(3):420–425. [PubMed] [Google Scholar]
  12. Hoofnagle J. H., Gerety R. J., Smallwood L. A., Barker L. F. Subtyping of hepatitis B surface antigen and antibody by radioimmunoassay. Gastroenterology. 1977 Feb;72(2):290–296. [PubMed] [Google Scholar]
  13. Lerner R. A., Green N., Alexander H., Liu F. T., Sutcliffe J. G., Shinnick T. M. Chemically synthesized peptides predicted from the nucleotide sequence of the hepatitis B virus genome elicit antibodies reactive with the native envelope protein of Dane particles. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3403–3407. doi: 10.1073/pnas.78.6.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. London W. T., Alter H. J., Lander J., Purcell R. H. Serial transmission in rhesus monkeys of an agent related to hepatitis-associated antigen. J Infect Dis. 1972 Apr;125(4):382–389. doi: 10.1093/infdis/125.4.382. [DOI] [PubMed] [Google Scholar]
  15. MacKay P., Pasek M., Magazin M., Kovacic R. T., Allet B., Stahl S., Gilbert W., Schaller H., Bruce S. A., Murray K. Production of immunologically active surface antigens of hepatitis B virus by Escherichia coli. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4510–4514. doi: 10.1073/pnas.78.7.4510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McAuliffe V. J., Purcell R. H., Gerin J. L. Type B hepatitis: a review of current prospects for a safe and effective vaccine. Rev Infect Dis. 1980 May-Jun;2(3):470–492. doi: 10.1093/clinids/2.3.470. [DOI] [PubMed] [Google Scholar]
  17. Muller J. Y. Protocol of analysis of the components present in mono- and polyspecific antisera. Bibl Haematol. 1976;42:137–158. doi: 10.1159/000399001. [DOI] [PubMed] [Google Scholar]
  18. Pasek M., Goto T., Gilbert W., Zink B., Schaller H., MacKay P., Leadbetter G., Murray K. Hepatitis B virus genes and their expression in E. coli. Nature. 1979 Dec 6;282(5739):575–579. doi: 10.1038/282575a0. [DOI] [PubMed] [Google Scholar]
  19. Peterson D. L., Nath N., Gavilanes F. Structure of hepatitis B surface antigen. Correlation of subtype with amino acid sequence and location of the carbohydrate moiety. J Biol Chem. 1982 Sep 10;257(17):10414–10420. [PubMed] [Google Scholar]
  20. Prince A. M., Ikram H., Hopp T. P. Hepatitis B virus vaccine: identification of HBsAg/a and HBsAg/d but not HBsAg/y subtype antigenic determinants on a synthetic immunogenic peptide. Proc Natl Acad Sci U S A. 1982 Jan;79(2):579–582. doi: 10.1073/pnas.79.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Purcell R. H., Gerin J. L. Hepatitis B vaccines. On the threshold. Am J Clin Pathol. 1978 Jul;70(1 Suppl):159–169. [PubMed] [Google Scholar]
  22. Shih J. W., Tan P. L., Gerin J. L. Antigenicity of the major polypeptides of hepatitis B surface antigen (HBsAg). J Immunol. 1978 Feb;120(2):520–525. [PubMed] [Google Scholar]
  23. Tiollais P., Charnay P., Vyas G. N. Biology of hepatitis B virus. Science. 1981 Jul 24;213(4506):406–411. doi: 10.1126/science.6264599. [DOI] [PubMed] [Google Scholar]
  24. Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H. M., Rutter W. J. Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen. Nature. 1979 Aug 30;280(5725):815–819. doi: 10.1038/280815a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES