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.
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]