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. 1984 Apr;81(8):2461–2465. doi: 10.1073/pnas.81.8.2461

Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin.

M Shapira, M Jibson, G Muller, R Arnon
PMCID: PMC345081  PMID: 6201857

Abstract

Four peptides have been synthesized, corresponding to different regions of the H3 influenza hemagglutinin, that are related to antigenic sites "A" and "B" of the molecule. The peptides consisted of the following sequences: 139-146, which forms the "loop" in the native hemagglutinin molecule, with either glycine or aspartic acid at position 144; 147-164, which contains part of antigenic determinant "B"; and 138-164, which comprises both the loop and the area 147-164. The peptides were conjugated to tetanus toxoid and used for immunization of rabbits and mice. All four conjugates elicited an immune response against the homologous peptides, but only the peptides 138-164 and 147-164 gave rise to antibodies that recognized and bound to the intact virus. Protection of mice against challenge infection with A/Eng/42/72 virus was achieved only by immunization with the conjugate (138-164)-TT, which led to partial protective effect. These data emphasize the role of molecular structure in determining the antigenic properties of synthetic peptides and indicate that the length of the peptide could be crucial for enforcing the right folding required to mimic the native structure.

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Selected References

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

  1. Arnon R., Maron E., Sela M., Anfinsen C. B. Antibodies reactive with native lysozyme elicited by a completely synthetic antigen. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1450–1455. doi: 10.1073/pnas.68.7.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bizzini B., Blass J., Turpin A., Raynaud M. Chemical characterization of tetanus toxin and toxoid. Amino acid composition, number of SH and S-S groups and N-terminal amino acid. Eur J Biochem. 1970 Nov;17(1):100–105. doi: 10.1111/j.1432-1033.1970.tb01141.x. [DOI] [PubMed] [Google Scholar]
  4. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971 Sep;8(9):871–874. doi: 10.1016/0019-2791(71)90454-x. [DOI] [PubMed] [Google Scholar]
  5. Fazekas de St Groth, Webster R. G. Disquisitions of Original Antigenic Sin. I. Evidence in man. J Exp Med. 1966 Sep 1;124(3):331–345. doi: 10.1084/jem.124.3.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Jackson D. C., Murray J. M., White D. O., Fagan C. N., Tregear G. W. Antigenic activity of a synthetic peptide comprising the "loop" region of influenza virus hemagglutinin. Virology. 1982 Jul 15;120(1):273–276. doi: 10.1016/0042-6822(82)90028-9. [DOI] [PubMed] [Google Scholar]
  8. Langbeheim H., Arnon R., Sela M. Antiviral effect on MS-2 coliphage obtained with a synthetic antigen. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4636–4640. doi: 10.1073/pnas.73.12.4636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Maoz A., Fuchs S., Sela M. On immunological cross-reactions between the synthetic ordered polypeptide (L-Pro-Gly-L-Pro)n and several collagens. Biochemistry. 1973 Oct 9;12(21):4246–4252. doi: 10.1021/bi00745a032. [DOI] [PubMed] [Google Scholar]
  10. Merrifield R. B. Automated synthesis of peptides. Science. 1965 Oct 8;150(3693):178–185. doi: 10.1126/science.150.3693.178. [DOI] [PubMed] [Google Scholar]
  11. Müller G. M., Shapira M., Arnon R. Anti-influenza response achieved by immunization with a synthetic conjugate. Proc Natl Acad Sci U S A. 1982 Jan;79(2):569–573. doi: 10.1073/pnas.79.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Spencer J. C., Ganguly R., Waldman R. H. Nonspecific protection of mice against influenza virus infection by local or systemic immunization with Bacille Calmette-Guérin. J Infect Dis. 1977 Aug;136(2):171–175. doi: 10.1093/infdis/136.2.171. [DOI] [PubMed] [Google Scholar]
  13. Suter M. A modified ELISA technique for anti-hapten antibodies. J Immunol Methods. 1982 Aug 27;53(1):103–108. doi: 10.1016/0022-1759(82)90244-7. [DOI] [PubMed] [Google Scholar]
  14. Wiley D. C., Wilson I. A., Skehel J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981 Jan 29;289(5796):373–378. doi: 10.1038/289373a0. [DOI] [PubMed] [Google Scholar]
  15. Wilson I. A., Skehel J. J., Wiley D. C. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature. 1981 Jan 29;289(5796):366–373. doi: 10.1038/289366a0. [DOI] [PubMed] [Google Scholar]

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