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Synthetic Peptides

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Vaccine Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 4))

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Abstract

Efforts to produce more stable and defined vaccines have concentrated on studying, in detail, the immune response to many infectious diseases in order to identify the antigenic sites on the pathogens that are involved in stimulating protective immumty. Armed with this knowledge, it is possible to mimic such sites by producing short chains of amino acids (peptides) and to use these as the basis for novel vaccines. The earliest documented work on peptide immunization is actually for a plant virus, tobacco mosaic virus. In 1963, Anderer (1) demonstrated that rabbit antibodies to an isolated hexapeptide fragment from the virus-coat protein coupled to bovine serum albumm would neutralize the infectious vn-us in culture. Two years later, he used a synthetically produced copy of the same peptide to confirm this observation. This was pioneering work, and it was over 10 years before the next example of a peptide that elicited antivirus antibody appeared following work by Sela and his colleagues (2) on a virus, MS2 bacteriophage, which infects bacteria. The emergence of more accessible techniques for sequencing proteins in 1977, coupled with the ability to synthesize readily peptides already developed in 1963, heralded a decade of intensive research into experimental peptide vaccines. The first demonstration that peptides could elicit protective immunity in vivo, in addition to neutralizing activity in vitro, was obtained using a peptide from the VP1 coat protein of foot-and-mouth disease virus (FMDV) in 1982, with the guinea pig as a laboratory animal model (3, 4).

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References

  1. Anderer, F. A. (1963) Versuch zur bestmuning der seralogisch termmaten gruppen des tobakmosaik vuus. Nuturforsch Tell B. 188, 1010–1014.

    Google Scholar 

  2. Langebeheim, H., Amon, R., and Sela, M. (1976) Antiviral effect of MS-2 cohphage obtained with a synthetic antigen. Proc. Natl. Acad. Sci. USA 73, 4636–4640.

    Article  Google Scholar 

  3. Bmle, J. L., Houghten, R. A., Alexander, H., Schmnick, T. M., Sutcliff, J. G., Lemer, R. A., Rowlands, D. J., and Brown, F. (1982) Protection against foot-andmouth diseaseb y nnmunization with a chemically synthesisedp eptide predicted from the viral nucleotrdes equence. Nature 298, 30–33.

    Article  Google Scholar 

  4. Pfaff, E., Mussgay, M., Bohm, H. O., Schalz, G. E., and Schaller, H. (1982) Antibodies against a preselected peptide recognize and neutralize foot and mouth disease virus. EMBO. J. 1, 869–874.

    PubMed  CAS  Google Scholar 

  5. DiMarchi, R., Brooke, G., Gale, C., Crocknell, V., Doel, T, and Mowat, N (1986) Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science 232, 639–641.

    Article  PubMed  CAS  Google Scholar 

  6. Broekhuijsen, M. P., Van Rijn, J. M. M., Blom, A. I. M., Pouwels, P H., Enger-Valk, B. E., Brown, F., and Francis, M. J. (1987) Fusion proteins with multiple copies of the maJor antigemc determmant of foot-and-mouth disease virus protect both the natural host and laboratory animals. J Gen. Viral 68, 3137–3143.

    Article  Google Scholar 

  7. Francis, M. J. (1990) Peptide vaccines for viral diseases. Sci. Prog. 74, 115–130.

    PubMed  CAS  Google Scholar 

  8. Merrifield, R. B. (1963) Solid phase peptide synthesis. 1. The synthesis of a tetrapeptide. J Am Chem. Soc. 85, 2149–2154

    Article  CAS  Google Scholar 

  9. Chang, C. D. and Meienhofer, J. (1978) Solid-phase peptide synthesis using nuld base cleavage of N-alpha-fluororenylmethyloxycarbonylammo acids, exemphfied by a synthesis of dihydrosomatostatm. Int J. Pept Protein Res. 11, 246–249.

    Article  PubMed  CAS  Google Scholar 

  10. Houghten, R. A. (1985) General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of mdividual ammo acids. Proc. Natl. Acad. Scz. USA 82, 5131–5135

    Article  CAS  Google Scholar 

  11. Francis, M. J., Hastings, G. Z., Clarke, B. E., Brown, A. L., Beddell, C. R., Rowlands, D. J., and Brown, F. (1990) Neutralizing antibodies to all seven serotypes of foot-and-mouth disease virus elicited by synthetic peptides. Immunology 69, 171–176.

    PubMed  CAS  Google Scholar 

  12. Devey, M. E., Bleasdale-Barr, K. M., Bird, P., and Amlot, P. L. (1990) Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunrsation with keyhole limpet haemocyanm. Immunology 70, 168–174.

    PubMed  CAS  Google Scholar 

  13. Davies, D, Chardhri, B, Stephens, M. D., Came, C. A., Willers, C., and Lachmann, P. J. (1990) The immunodominance of epitopes within the transmembrane protein (gp41) of human mnnunodeficiency vnus type 1 may be determined by the host’s previous exposure to similar epttopes on unrelated antigens. J. Gen Vzrol 71, 1975–1983.

    Article  Google Scholar 

  14. Katz, D. H., Paul, W. E., Goidl, E. A., and Benacerraf, B. (1970) Carrier function in anti-hapten immune responses. 1. Enhancement of primary and secondary antihapten antibody responses by carrier pre-lmmunisation. J Exp. Med. 132, 261–282.

    Article  PubMed  CAS  Google Scholar 

  15. Gupta, S. G., Hengartner, H., and Zmkernagel, R M. (1986) Primary antibody responses to a well-defined and unique hapten are not enhanced by pre-mmumisation with carrier: analysis in a viral model. Proc Natl. Acad. Scz USA 83, 2604–2608.

    Article  CAS  Google Scholar 

  16. Herzenberg, L. A., Tokuhisa, T., and Herzenberg, L. A. (1980) Carrier-priming leads to hapten-specific suppression. Nature 285, 664–667.

    Article  PubMed  CAS  Google Scholar 

  17. Dyrberg, T. and Oldstone, M. B. (1986) Peptides as antigens, importance of onentation. J. Exp. Med. 164, 1344–1349.

    Article  PubMed  CAS  Google Scholar 

  18. Palfreyman, J. W., Aitcheson, T. C. and Taylor, P. (1984) Guidelmes for the production of polypeptide specific antisera using small synthetic oltgopeptides as immunogens. J. Immunol Methods 75, 383–393.

    Article  PubMed  CAS  Google Scholar 

  19. Francis, M. J., Fry, C. M., Rowlands, D. J., Brown, F., Bittle, J. L., Houghten, R. A., and Lerner, R. A. (1985) Immunological pnming with synthetic peptides of foot-and-mouth disease virus. J Gen Vzrol 66, 2347–2354.

    Article  CAS  Google Scholar 

  20. Francis, M. J., Fry, C. M., Rowlands, D. J., Bittle, J. L., Houghten, R. A., Lerner, R. A., and Brown, F. (1987) Immune response to uncoupled peptides of foot-andmouth disease virus. Immunology 61, 1–6.

    PubMed  CAS  Google Scholar 

  21. DeLisi, C. and Berzofsky, J. A. (1987) T-cell antigemc sites tend to be amphipathic structures. Proc. Natl. Acad. Sci. USA 82, 7048–7052.

    Article  Google Scholar 

  22. Rothbard, J. B. (1986) Peptides and the cellular immune response. Ann. Inst. Pasteur 137E, 518–526.

    Article  CAS  Google Scholar 

  23. Rothbard, J. B. and Taylor, W. R. (1988) A sequence pattern common to T cell epitopes. EMBO J. 7, 93–100.

    PubMed  CAS  Google Scholar 

  24. Leclerc, C., Przewlocki, G., Schutze, M., and Chedid, L. (1987) A synthetic vaccine constructed by co-polymerization of B and T cell determinants. Eur. J Immunol. 17, 269–273.

    Article  PubMed  CAS  Google Scholar 

  25. Good, M. F., Maloy, W. F., Lunde, M. N., Margalit, H., Cornette, J. L., Smith, G L., Moss, B., Miller, L. H., and Berzofsky, J. A. (1987) Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protem. Science 235, 1059–1062.

    Article  PubMed  CAS  Google Scholar 

  26. Borras-Cuesta, F., Petit-Camurdan, A., and Fedon, Y. (1987) Engmeering of immunogemc peptides by co-linear synthesis of determinants recogmsed by B and T cells. Eur. J Immunol. 17, 1213–1215.

    Article  PubMed  CAS  Google Scholar 

  27. Francis, M. J., Hastings, G. Z., Syred, A. D., McGinn, B., Brown, F., and Rowlands, D. J. (1987) Nonresponsiveness to a foot-and-mouth disease virus synthetic peptide overcome by addition of foreign helper T-cell determinants. Nature 330, 168–169.

    Article  PubMed  CAS  Google Scholar 

  28. Milich, D. R., Hughes, J. L., McLachlan, A., Thornton, G. B., and Moriarty, A. (1988) Hepatitis B synthetrc immunogen comprised of nucleocapsid T-cell sites and an envelope B-cell epitope. Proc. Natl. Acad. Sci. USA 85, 1610–1614.

    Google Scholar 

  29. Patarroyo, M. E., Romero, P., Torres, M. L., Clavijo, P., Moreno, A., Martinez, A, et al. (1987) Induction of protective immunity against experimental infection with malaria using synthetic peptides. Nature 328, 629–632

    Article  PubMed  CAS  Google Scholar 

  30. Bittle, J. L., Worrell, P., Houghten, R. A., Lerner, R. A., Rowlands, D. J. and Brown, F. (1984) Immunization against foot-and-mouth disease with a chemically synthesized peptide, in Modern Approaches to Vaccines (Chanock, R. M. and Lerner, R. A., eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp, 103–108.

    Google Scholar 

  31. Francis, M. J. (1991) Enhanced immunogenicity of recombinant and synthetic peptide vaccines, in Vaccines: Recent Trends and Progress. NATO ASI Series Vaccines vol. 215, pp. 13–23.

    CAS  Google Scholar 

  32. Tam, J. P. (1988) Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigemc peptide system. Proc. Natl. Acad. Sci. USA 85, 5409–5413.

    Article  PubMed  CAS  Google Scholar 

  33. Posnett, D. N., McGrath, H., and Tam, J. P. (1988) A novel method for producing anti-peptide antibodies: production of site specific antibodies to the T cell antigen receptor μ-chain J. Biol. Chem. 263, 1719–1725

    PubMed  CAS  Google Scholar 

  34. Tam, J. P. (1989) Multiple antigen peptide system: a novel design for peptide-based antibody and vaccine, in Vaccines 90: Modern Approaches to New Vacanes Including Prevention of AIDS (Lerner, R. A., Ginsberg, H., Chanock, R. M., and Brown, F., eds.), Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp. 21–25.

    Google Scholar 

  35. Francis, M. J., Fry, C. M., Rowlands, D. J., and Brown, F. (1988) Qualitative and quantitative differences in the immune response to foot-and-mouth disease virus antigens and synthetic peptide. J. Gen. Viral. 69, 2483–2491.

    Article  CAS  Google Scholar 

  36. Francis, M. J., Hastings, G. Z., Brown, F., McDermed, J., Lu, Y. A., and Tam, J. P. (1991) Immunological evaluation of the multiple antigen peptide (MAP) system using a maJor rwnunogenic site of foot-and-mouth disease virus. Immunology 73, 249–254

    PubMed  CAS  Google Scholar 

  37. Kennedy, R. C., Dressman, G. R., Sparrow, J. T., Culwell, A. R., Sanchez, Y., Ionescu-Matiu, E., Blame Hollinger, F., and Melmck, J. L. (1983) Inhibition of a common human ant1 hepatitis B surface antigen idiotype by a cyclic synthetic peptide. J Virol. 46, 653–655.

    PubMed  CAS  Google Scholar 

  38. Schulze-Gahmen, U., Klenk, H. D, and Beyreuther, K. (1986) Immunogemcity of loop structured short synthetic peptides mimicking the antigen site A of mfluenza vnus haemagglutinm. Eur. J. Blochem. 159, 283–289.

    Article  CAS  Google Scholar 

  39. Fergusen, M., Evans, D. M. A., Magrath, D. I., Minor, P. D., Almond, J. W., and Schild, G. C. (1985) Induction by synthetic peptides of broadly reactive, type specific neutrahzing antibody to poliovuus type 3. Vzrology 143, 505–515.

    Article  Google Scholar 

  40. Satterthwait, A. C., Arrhenius, T., Hagopian, R. A., Zavala, F., Nussenzweig, V., and Lerner, R. A. (1988) Conformational restriction of peptidyl immunogens with covalent replacements for the hydrogen bond. Vaccine 6, 99–103.

    Article  PubMed  CAS  Google Scholar 

  41. Francis, M. J. (1991) Enhanced immunogemcity of recombinant and synthetic pepttde vaccmes, in Vaccines Recent Trends and Progress. NATO ASI Series Vaccrnes, vol. 215, pp 13–24.

    CAS  Google Scholar 

  42. Francis, M J. (1992) Use of hepatitis B core as a vehicle for presenting viral antigens. Rev. Med. Vrrol. 2, 225–231.

    Article  Google Scholar 

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© 1996 Humana Press Inc, Totowa, NJ

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Francis, M.J. (1996). Synthetic Peptides. In: Robinson, A., Farrar, G.H., Wiblin, C.N. (eds) Vaccine Protocols. Methods in Molecular Medicine™, vol 4. Humana Press. https://doi.org/10.1385/0-89603-334-1:75

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  • DOI: https://doi.org/10.1385/0-89603-334-1:75

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-334-4

  • Online ISBN: 978-1-59259-588-4

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