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. 1985 Aug;49(2):312–319. doi: 10.1128/iai.49.2.312-319.1985

Marked enhancement in vivo of adjuvant activity of muramyl dipeptide to protein antigens and to synthetic weak immunogens with monoclonal anti-muramyl dipeptide antibodies.

G M Bahr, D S Tello, L A Chedid
PMCID: PMC262016  PMID: 4018873

Abstract

Priming of mice with complexes of antigen coupled to muramyl dipeptide and monoclonal anti-muramyl dipeptide antibodies enhanced the adjuvant activity of muramyl dipeptide on the humoral response to the antigen. The enhancement did not occur with free (uncoupled) muramyl dipeptide and required the presence of an adjuvant-active hapten within the complex as well as the Fc fragment of the monoclonal antibody. This system proved highly effective in eliciting antibodies to synthetic weak immunogens whereas muramyl dipeptide, on its own, exerts very little or no adjuvant activity. The effect was not due to a general polyclonal activation and was restricted to the antigen coupled to the synthetic adjuvant. Possible pathways involved in this phenomenon are discussed.

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Selected References

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  1. Abrahams S., Phillips R. A., Miller R. G. Inhibition of the immune response by 7S antibody mechanism and site of action. J Exp Med. 1973 Apr 1;137(4):870–892. doi: 10.1084/jem.137.4.870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adam A., Petit J. F., Lefrancier P., Lederer E. Muramyl peptides. Chemical structure, biological activity and mechanism of action. Mol Cell Biochem. 1981 Dec 4;41:27–47. doi: 10.1007/BF00225295. [DOI] [PubMed] [Google Scholar]
  3. Audibert F., Jolivet M., Chedid L., Arnon R., Sela M. Successful immunization with a totally synthetic diphtheria vaccine. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5042–5046. doi: 10.1073/pnas.79.16.5042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bahr G. M., Carelli C., Audibert F., Modabber F., Chedid L. Analysis of the antigenic relationship of various derivatives of n-acetyl-muramyl-l-ala-d-isoglutamine (MDP), using anti-MDP antibodies. Mol Immunol. 1982 May;19(5):737–745. doi: 10.1016/0161-5890(82)90375-3. [DOI] [PubMed] [Google Scholar]
  5. Bahr G. M., Eshhar Z., Ben-Yitzhak R., Modabber F. Z., Arnon R., Sela M., Chedid L. Monoclonal antibodies to the synthetic adjuvant muramyl dipeptide: characterization of the specificity. Mol Immunol. 1983 Jul;20(7):745–752. doi: 10.1016/0161-5890(83)90052-4. [DOI] [PubMed] [Google Scholar]
  6. Bahr G. M., Rook G. A., Moreno E., Lydyard P. M., Modabber F. Z., Stanford J. L. Use of the ELISA to screen for anti-thymocyte and anti-beta 2-microglobulin antibodies in leprosy and SLE. Immunology. 1980 Dec;41(4):865–873. [PMC free article] [PubMed] [Google Scholar]
  7. Beachey E. H., Stollerman G. H., Chiang E. Y., Chiang T. M., Seyer J. M., Kang A. H. Purification and properties of M protein extracted from group A streptococci with pepsin: covalent structure of the amino terminal region of type 24 M antigen. J Exp Med. 1977 Jun 1;145(6):1469–1483. doi: 10.1084/jem.145.6.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carelli C., Audibert F., Gaillard J., Chedid L. Immunological castration of male mice by a totally synthetic vaccine administered in saline. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5392–5395. doi: 10.1073/pnas.79.17.5392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Eshhar Z., Ofarim M., Waks T. Generation of hybridomas secreting murine reaginic antibodies of anti-DNP specificity. J Immunol. 1980 Feb;124(2):775–780. [PubMed] [Google Scholar]
  12. Galelli A., Chedid L. Modulation of myelopoiesis in vivo by synthetic adjuvant-active muramyl peptides: induction of colony-stimulating activity and stimulation of stem cell proliferation. Infect Immun. 1983 Dec;42(3):1081–1085. doi: 10.1128/iai.42.3.1081-1085.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gordon J., Murgita R. A. Suppression and augmentation of the primary in vitro immune response by different classes of antibodies. Cell Immunol. 1975 Feb;15(2):392–402. doi: 10.1016/0008-8749(75)90017-9. [DOI] [PubMed] [Google Scholar]
  14. Harte P. G., Cooke A., Playfair J. H. Specific monoclonal IgM is a potent adjuvant in murine malaria vaccination. Nature. 1983 Mar 17;302(5905):256–258. doi: 10.1038/302256a0. [DOI] [PubMed] [Google Scholar]
  15. Janeway C. A., Jr The mechanism of a hapten-specific helper effect in mice. J Immunol. 1973 Oct;111(4):1250–1256. [PubMed] [Google Scholar]
  16. Jolivet M., Audibert F., Beachey E. H., Tartar A., Gras-Masse H., Chedid L. Epitope specific immunity elicited by a synthetic streptococcal antigen without carrier or adjuvant. Biochem Biophys Res Commun. 1983 Dec 16;117(2):359–366. doi: 10.1016/0006-291x(83)91208-1. [DOI] [PubMed] [Google Scholar]
  17. Kireszenbaum F., Ferraresi R. W. Enhancement of host resistance against Trypanosoma cruzi infection by the immunoregulatory agent muramyl dipeptide. Infect Immun. 1979 Jul;25(1):273–278. doi: 10.1128/iai.25.1.273-278.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kotani S., Kinoshita F., Morisaki I., Shimono T., Okunaga T., Takada H., Tsujimoto M., Watanabe Y., Kato K., Shiba T. Immunoadjuvant activities of synthetic 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with special reference to the effect of its administration with liposomes. Biken J. 1977 Dec;20(3-4):95–103. [PubMed] [Google Scholar]
  19. Krueger J. M., Walter J., Karnovsky M. L., Chedid L., Choay J. P., Lefrancier P., Lederer E. Muramyl peptides. Variation of somnogenic activity with structure. J Exp Med. 1984 Jan 1;159(1):68–76. doi: 10.1084/jem.159.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kulberg A. J., Bartova L. M., Evnin D. N. Further studies of the adjuvant properties of homologous IgG split products: mode of action of F(ab')2 and related fragments. Immunology. 1978 Feb;34(2):199–206. [PMC free article] [PubMed] [Google Scholar]
  21. Leclerc C., Bahr G. M., Chedid L. Marked enhancement of macrophage activation induced by synthetic muramyl dipeptide (MDP) conjugate using monoclonal anti-MDP antibodies. Cell Immunol. 1984 Jul;86(2):269–277. doi: 10.1016/0008-8749(84)90381-2. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Maillard J., Bloom B. R. Immunological adjuvants and the mechanism of cell cooperation. J Exp Med. 1972 Jul 1;136(1):185–190. doi: 10.1084/jem.136.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Merser C., Sinay P., Adam A. Total synthesis and adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1316–1322. doi: 10.1016/0006-291x(75)90503-3. [DOI] [PubMed] [Google Scholar]
  25. Morgan E. L., Shields J. E., Campbell C. S., Barton R. L., Koppel G. A., Weigle W. O. Synthetic Fc peptide-mediated regulation of the immune response. I. Characterization of the immunomodulating properties of a synthetic 23-amino acid peptide derived from the sequence of the CH3 domain of human IgG1. J Exp Med. 1983 Mar 1;157(3):947–956. doi: 10.1084/jem.157.3.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murgita R. A., Vas S. I. Specific antibody-mediated effect on the immune response. Suppression and augmentation of the primary immune response in mice by different classes of antibodies. Immunology. 1972 Mar;22(3):319–331. [PMC free article] [PubMed] [Google Scholar]
  27. Nakane P. K., Kawaoi A. Peroxidase-labeled antibody. A new method of conjugation. J Histochem Cytochem. 1974 Dec;22(12):1084–1091. doi: 10.1177/22.12.1084. [DOI] [PubMed] [Google Scholar]
  28. Neveu P. J., Borduas A. G. Modulation of the immune response by passive antibodies. I. Anti-hapten antibodies enhanced delayed hypersensitivity to the carrier and depressed antibody synthesis to the hapten. Int Arch Allergy Appl Immunol. 1975;48(5):698–705. doi: 10.1159/000231357. [DOI] [PubMed] [Google Scholar]
  29. Neveu P. J., Micusan V. V., Fafard A., Borduas A. G. Modulation of the immune response by passive antibodies. IV. Effects of IgG1 and IgG2 anti-hapten antibodies. Immunology. 1978 Jul;35(1):129–132. [PMC free article] [PubMed] [Google Scholar]
  30. RAMACHANDRAN L. K., SASTRY L. V. Spectrometric evaluation of the approximate pK of the carboxyl group in 2,4-dinitrophenyl-amino acids. Biochemistry. 1962 Jan;1:75–78. doi: 10.1021/bi00907a012. [DOI] [PubMed] [Google Scholar]
  31. REISSIG J. L., STORMINGER J. L., LELOIR L. F. A modified colorimetric method for the estimation of N-acetylamino sugars. J Biol Chem. 1955 Dec;217(2):959–966. [PubMed] [Google Scholar]
  32. Sone S., Fidler I. J. In vitro activation of tumoricidal properties in rat alveolar macrophages by synthetic muramyl dipeptide encapsulated in liposomes. Cell Immunol. 1981 Jan 1;57(1):42–50. doi: 10.1016/0008-8749(81)90118-0. [DOI] [PubMed] [Google Scholar]
  33. Uhr J. W., Möller G. Regulatory effect of antibody on the immune response. Adv Immunol. 1968;8:81–127. doi: 10.1016/s0065-2776(08)60465-4. [DOI] [PubMed] [Google Scholar]
  34. Voisin G. A. Role of antibody classes in the regulatory facilitation reaction. Immunol Rev. 1980;49:3–59. doi: 10.1111/j.1600-065x.1980.tb00425.x. [DOI] [PubMed] [Google Scholar]
  35. Walker J. G., Siskind G. W. Studies on the control of antibody synthesis. Effect of antibody affinity upon its ability to suppress antibody formation. Immunology. 1968 Jan;14(1):21–28. [PMC free article] [PubMed] [Google Scholar]

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