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. 1980 Nov;77(11):6769–6772. doi: 10.1073/pnas.77.11.6769

Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity.

R Arnon, M Sela, M Parant, L Chedid
PMCID: PMC350370  PMID: 6935684

Abstract

In a previous study we demonstrated that antiviral response against the coliphage MS-2 can be elicited by immunization with a synthetic antigen consisting of a conjugate (P2-A -- L) of a synthetic fragment (P2) of the virus coat protein attached to a synthetic polymeric carrier. The antiviral response was induced when the antigen was administered in complete Freund's adjuvant or when it was administered in incomplete adjuvant, provided that a peptidoglycan was covalently attached to it. In the present study we demonstrate the adjuvant effect of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in this system. Immunization with a mixture of MDP and P2-A -- L brought about only slight enhancement in the titer of neutralizing antibodies, as compared to the immunization with P2-A -- L in saline. The best results were achieved when the MDP was chemically conjugated to P2-A -- L. This completely synthetic material, when administered in aqueous solution, yielded highly inactivating antiserum with a titer similar to that obtained with complete Freund's adjuvant in the absence of MDP. MDP-P2-A -- L elicited also a humoral immune response to MDP, but with much lower titer than that induced by complete Freund's adjuvant containing P2-A -- L only. It was also observed that the capacity of MDP-P2-A -- L to increase resistance against infection was more than a 100-fold greater than that of unconjugated MDP.

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Selected References

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

  1. Adam A., Ciorbaru R., Petit J. F., Lederer E. Isolation and properties of a macromolecular, water-soluble, immuno-adjuvant fraction from the cell wall of Mycobacterium smegmatis. Proc Natl Acad Sci U S A. 1972 Apr;69(4):851–854. doi: 10.1073/pnas.69.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnon R., Bustin M., Calef E., Chaitchik S., Haimovich J., Novik N., Sela M. Immunological cross-reactivity of antibodies to a synthetic undecapeptide analogous to the amino terminal segment of carcinoembryonic antigen, with the intact protein and with human sera. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2123–2127. doi: 10.1073/pnas.73.6.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Arnon R. Site-directed tumor chemotherapy. Compr Ther. 1978 Apr;4(4):68–73. [PubMed] [Google Scholar]
  5. Chedid L., Audibert F., Johnson A. G. Biological activities of muramyl dipeptide, a synthetic glycopeptide analogous to bacterial immunoregulating agents. Prog Allergy. 1978;25:63–105. [PubMed] [Google Scholar]
  6. Chedid L., Parant M., Parant F., Audibert F., Lefrancier F., Choay J., Sela M. Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly(DL-alanine)--poly(L-lysine) carrier. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6557–6561. doi: 10.1073/pnas.76.12.6557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chedid L., Parant M., Parant F., Lefrancher P., Choay J., Lederer E. Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs. Proc Natl Acad Sci U S A. 1977 May;74(5):2089–2093. doi: 10.1073/pnas.74.5.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ellouz F., Adam A., Ciorbaru R., Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1317–1325. doi: 10.1016/0006-291x(74)90458-6. [DOI] [PubMed] [Google Scholar]
  9. Emtage J. S., Tacon W. C., Catlin G. H., Jenkins B., Porter A. G., Carey N. H. Influenza antigenic determinants are expressed from haemagglutinin genes cloned in Escherichia coli. Nature. 1980 Jan 10;283(5743):171–174. doi: 10.1038/283171a0. [DOI] [PubMed] [Google Scholar]
  10. Eshhar Z., Strassmann G., Waks T., Mozes E. In vitro and in vivo induction of effector T cells mediating DTH responses to a protein and a synthetic polypeptide antigen. Cell Immunol. 1979 Oct;47(2):378–389. doi: 10.1016/0008-8749(79)90347-2. [DOI] [PubMed] [Google Scholar]
  11. Gesteland R. F., Spahr P. F. A new procedure for the preparation of highly labeled intact 32P RNA from bacteriophage R-17. Biochem Biophys Res Commun. 1970 Dec 9;41(5):1267–1272. doi: 10.1016/0006-291x(70)90224-x. [DOI] [PubMed] [Google Scholar]
  12. Klinman N. R., Pickard A. R., Sigal N. H., Gearhart P. J., Metcalf E. S., Pierce S. K. Assessing B cell diversification by antigen receptor and precursor cell analysis. Ann Immunol (Paris) 1976 Jun-Jul;127(3-4):489–502. [PubMed] [Google Scholar]
  13. Kotani S., Watanabe Y., Kinoshita F., Shimono T., Morisaki I. Immunoadjuvant activities of synthetic N-acetyl-muramyl-peptides or -amino acids. Biken J. 1975 Jun;18(2):105–111. [PubMed] [Google Scholar]
  14. Langbeheim H., Arnon R., Sela M. Adjuvant effect of a peptidoglycan attached covalently to a synthetic antigen provoking anti-phage antibodies. Immunology. 1978 Oct;35(4):573–579. [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Lefrancier P., Choay J., Derrien M., Lederman I. Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response, and of some n-acetyl-muramyl-peptide analogs. Int J Pept Protein Res. 1977;9(4):249–257. doi: 10.1111/j.1399-3011.1977.tb03488.x. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Mozes E., Sela M., Chedid L. Efficient genetically controlled formation of antibody to a synthetic antigen [poly(LTyr, LGlu)-poly(DLAla)- -poly(LLys)] covalently bound to a synthetic adjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine). Proc Natl Acad Sci U S A. 1980 Aug;77(8):4933–4937. doi: 10.1073/pnas.77.8.4933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mozes E., Shearer G. M. Genetic control of immune responses. Curr Top Microbiol Immunol. 1972;59:167–200. doi: 10.1007/978-3-642-65444-2_6. [DOI] [PubMed] [Google Scholar]
  20. Nagai Y., Akiyama K., Suzuki K., Kotani S., Watanabe Y., Shimono T., Shiba T., Kusumoto S., Ikuta F., Takeda S. Minimum structural requirements for encephalitogen and for adjuvant in the induction of experimental allergic encephalomyelitis. Cell Immunol. 1978 Jan;35(1):158–167. doi: 10.1016/0008-8749(78)90135-1. [DOI] [PubMed] [Google Scholar]
  21. Nguyen-Huy H., Nauciel C., Wermuth C. G. Immunochemical study of the peptidoglycan of gram-negative bacteria. Eur J Biochem. 1976 Jun 15;66(1):79–84. doi: 10.1111/j.1432-1033.1976.tb10427.x. [DOI] [PubMed] [Google Scholar]
  22. Paterson P. Y. Experimental allergic encephalomyelitis and autoimmune disease. Adv Immunol. 1966;5:131–208. doi: 10.1016/s0065-2776(08)60273-4. [DOI] [PubMed] [Google Scholar]
  23. Reichert C. M., Carelli C., Jolivet M., Audibert F., Lefrancier P., Chedid L. Synthesis of conjugates containing N-acetylmuramyl-L-alanyl-D-isoglutaminyl (MDP). Their use as hapten-carrier systems. Mol Immunol. 1980 Mar;17(3):357–363. doi: 10.1016/0161-5890(80)90056-5. [DOI] [PubMed] [Google Scholar]
  24. SELA M., ARNON R. A specific synthetic polypeptide antigen. Biochim Biophys Acta. 1960 May 20;40:382–384. doi: 10.1016/0006-3002(60)91377-9. [DOI] [PubMed] [Google Scholar]
  25. Shearer G. M., Mozes E., Sela M. Contribution of different cell types to the genetic control of immune responses as a function of the chemical nature of the polymeric side chains (poly-L-prolyl and poly-DL-alanyl) of synthetic immunogens. J Exp Med. 1972 May 1;135(5):1009–1027. doi: 10.1084/jem.135.5.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]

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