Skip to main content

Immune and Antiviral Effects of the Synthetic Immunomodulator Murabutide

Molecular Basis and Clinical Potential

  • Chapter
Vaccine Adjuvants

Part of the book series: Infectious Disease ((ID))

Abstract

The field of immunomodulation started with the concept of vaccination to protect against infectious diseases, an approach successfully employed by Edward Jenner over 200 years ago. From this initial concept and based on the progress in understanding the functions of the immune system, it became evident that several immune pathways could be regulated, either positively or negatively, to restore the disrupted immune homeostasis in a wide array of human diseases. Today, therapeutic approaches aimed at modulating immune mechanisms extend from interventions in cancer and organ transplantation to reach infectious, autoimmune, immunodeficiency, and neurological diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Freund J. The mode of action of immunologic adjuvants. Adv Tuberc Res 1956;7:130–148.

    Google Scholar 

  2. Azuma I, Kishimoto S, Yamamura Y, Petit J-F. Adjuvanticity of mycobacterial cell wall. Jpn J Microbiol 1971;15:193–197.

    PubMed  CAS  Google Scholar 

  3. Ellouz F, Adam A, Ciorbaru R, Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun 1974;59:1317–1325.

    Article  PubMed  CAS  Google Scholar 

  4. Lederer E. Natural and synthetic immunomodulators derived from the mycobacterial cell wall. In: Bizzini B, Bonmassar E, eds. Advances in Immunomodulation. Roma: Pythagora Press, 1988, pp. 9–36.

    Google Scholar 

  5. Bahr GM, Darcissac E, Bevec D, Dukor P, Chedid L. Immunopharmacological activities and clinical development of muramyl peptides with particular emphasis on murabutide. Int J Immunopharmacol 1995;17:117–131.

    Article  PubMed  CAS  Google Scholar 

  6. Waters RV, Terrell TG, Jones GH. Uveitis induction in the rabbit by muramyl dipeptides. Infect Immun 1986;51:816–825.

    PubMed  CAS  Google Scholar 

  7. Chedid L, Audibert F, Lefrancier P, Choay J, Lederer E. Modulation of the immune response by a synthetic adjuvant and analogs. Proc Natl Acad Sci USA 1976;73:2472–2475.

    Article  PubMed  CAS  Google Scholar 

  8. Lefrancier P, Derrien M, Jamet X, et al. Apyrogenic, adjuvant-active N-acetylmuramyl-dipeptides. J Med Chem 1982;25:87–90.

    Article  PubMed  CAS  Google Scholar 

  9. Werner GH, Jolles P. Immunostimulating agents: what next? A review of their present and potential medical applications. Eur J Biochem 1996;242:1–19.

    Article  PubMed  CAS  Google Scholar 

  10. Azuma I, Otani T. Potentiation of host defense mechanism against infection by a cytokine inducer, an acyl-MDP derivative, MDP-Lys(L18) (romurtide) in mice and humans. Med Res Rev 1994;14:401–414.

    Article  PubMed  CAS  Google Scholar 

  11. 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 USA 1977;74:2089–2093.

    Article  PubMed  CAS  Google Scholar 

  12. Phillips NC, Chedid L. Muramyl peptides and liposomes. In: Gregoriadis GE, ed. Liposomes as Drug Carriers. Chichester: John Wiley and Sons Ltd, 1988, pp. 243–259.

    Google Scholar 

  13. Parant M. Muramyl peptides as enhancers of host resistance to bacterial infections. In: Majde JA, ed. Immunopharmacology of Infectious Diseases: Vaccine Adjuvants and Modulators of Non-Specific Resistance. New-York: Alan R. Liss, Inc., 1987, pp. 235–244.

    Google Scholar 

  14. Parant M, Chedid L. Muramyl dipeptides. In: Bray MA, Morley J, eds. Handbook of Experimental Pharmacology, vol. 85. Berlin: Springer-Verlag, 1988, pp. 503–516.

    Google Scholar 

  15. Bahr GM, Chedid L. Immunological activities of muramyl peptides. Fed Proc 1986;45:2541–2544.

    PubMed  CAS  Google Scholar 

  16. Souvannavong V, Brown S, Adam A. The synthetic immunomodulator muramyl dipeptide (MDP) can stimulate activated B cells. Mol Immunol 1988;25:385–391.

    Article  PubMed  CAS  Google Scholar 

  17. Heinzelmann M, Mercer-Jones MA, Gardner SA, Wilson MA, Polk HC. Bacterial cell wall products increase monocyte HLA-DR and ICAM-1 without affecting lymphocyte CD18 expression. Cell Immunol 1997;176:127–134.

    Article  PubMed  CAS  Google Scholar 

  18. Warren HS, Chedid LA. Future prospects for vaccine adjuvants. Crit Rev Immunol 1988;8:83–101.

    PubMed  CAS  Google Scholar 

  19. Ayabe T, Satchell DP, Wilson CL, Parks WC, Selsted ME, Ouellette AJ. Secretion of microbicidal alpha-defensins by intestinal Paneth cells in response to bacteria. Nat Immunol 2000;1:113–118.

    Article  PubMed  CAS  Google Scholar 

  20. Polk HC Jr, Lamont PM, Galland RB. Containment as a mechanism of nonspecific enhancement of defenses against bacterial infection. Infect Immun 1990;58:1807–1811.

    PubMed  Google Scholar 

  21. O’Reilly T, Zak O. Enhancement of the effectiveness of antimicrobial therapy by muramyl peptide immunomodulators. Clin Infect Dis 1992;14:1100–1109.

    PubMed  CAS  Google Scholar 

  22. Asano T, Kleinerman ES. Liposome-encapsulated MTP-PE: a novel biologic agent for cancer therapy. J Immunother 1993;14:286–292.

    Article  CAS  Google Scholar 

  23. Kricek F, Zunic M, Ruf C, De Jong G, Dukor P, Bahr GM. Suppression of in vivo IgE and tissue IL-4 mRNA induction by SDZ 280.636, a synthetic muramyl dipeptide derivative. Immunopharmacology 1997;36:27–39.

    Article  PubMed  Google Scholar 

  24. Zunic M, Bahr GM, Mudde GC, Meingassner JG, Lam C. MDP(Lysyl)GDP, a nontoxic muramyl dipeptide derivative, inhibits cytokine production by activated macrophages and protects mice from phorbol ester-and oxazolone-induced inflammation. J Invest Dermatol 1998;111:77–82.

    Article  PubMed  CAS  Google Scholar 

  25. Galelli A, Chedid L. Modulation of myelopoiesis in vivo by synthetic adjuvantactive muramyl peptides: induction of colony-stimulating activity and stimulation of stem cell proliferation. Infect Immun 1983;42:1081–1085.

    PubMed  CAS  Google Scholar 

  26. Azuma I. Development of the cytokine inducer romurtide: experimental studies and clinical application. Trends Pharmacol Sci 1992;13:425–428.

    Article  PubMed  CAS  Google Scholar 

  27. Namba K, Nitanai H, Otani T, Azuma I. Romurtide, a synthetic muramyl dipeptide derivative, accelerates peripheral platelet recovery in nonhuman primate chemotherapy model. Vaccine 1996;14:1322–1326.

    Article  PubMed  CAS  Google Scholar 

  28. Phillips NC, Tsoukas C, Chedid L. Abrogation of azidothymidine-induced bone marrow toxicity by free and liposomal muramyl dipeptide. In: Masihi KN, Lange W, eds. Immunotherapeutic Prospects of Infectious Diseases. Berlin: Springer-Verlag, 1990, pp. 135–139.

    Google Scholar 

  29. Chedid LA, Parant MA, Audibert FM, et al. Biological activity of a new synthetic muramyl peptide adjuvant devoid of pyrogenicity. Infect Immun 1982;35:417–424.

    PubMed  CAS  Google Scholar 

  30. Riveau GJ, Chedid L. Comparison of the immuno-and neuropharmacological activities of MDP and murabutide. In: Majde JA, ed. Immunopharmacology of Infectious Diseases: Vaccine Adjuvants and Modulators of Non-Specific Resistance. New-York: Alan R Liss, Inc, 1987, pp. 213–222.

    Google Scholar 

  31. Krueger JM, Walter J, Karnovsky ML, et al. Muramyl peptides. Variation of somnogenic activity with structure. J Exp Med 1984;159:68–76.

    Article  PubMed  CAS  Google Scholar 

  32. McAdam KP, Foss NT, Garcia C, et al. Amyloidosis and the serum amyloid A protein response to muramyl dipeptide analogs and different mycobacterial species. Infect Immun 1983;39:1147–1154.

    PubMed  CAS  Google Scholar 

  33. Koga T, Kakimoto K, Hirofuji T, Kotani S, Sumiyoshi A, Saisho K. Muramyl dipeptide induces acute joint inflammation in the mouse. Microbiol Immunol 1986;30:717–723.

    PubMed  CAS  Google Scholar 

  34. Zidek Z. Differences in proinflammatory activity of several immunomodulatory derivatives of muramyl dipeptide (MDP) with special reference to the mechanism of the MDP effects. Agents Actions 1992;36:136–145.

    Article  PubMed  CAS  Google Scholar 

  35. Byars NE. Two adjuvant-active muramyl dipeptide analogs induce differential production of lymphocyte-activating factor and a factor causing distress in guinea pigs. Infect Immun 1984;44:344–350.

    PubMed  CAS  Google Scholar 

  36. Kong YC, Audibert F, Giraldo AA, Rose NR, Chedid L. Effects of natural or synthetic microbial adjuvants on induction of autoimmune thyroiditis. Infect Immun 1985;49:40–45.

    PubMed  CAS  Google Scholar 

  37. Chang YH, Pearson CM, Chedid L. Adjuvant polyarthritis. V. Induction by N-acetylmuramyl-L-alanyl-D-isoglutamine, the smallest peptide subunit of bacterial peptidoglycan. J Exp Med 1981;153:1021–1026.

    Article  PubMed  CAS  Google Scholar 

  38. Audibert FM, Przewlocki G, Leclerc CD, et al. Enhancement by murabutide of the immune response to natural and synthetic hepatitis B surface antigens. Infect Immun 1984;45:261–266.

    PubMed  CAS  Google Scholar 

  39. Przewlocki G, Audibert F, Jolivet M, Chedid L, Kent SB, Neurath AR. Production of antibodies recognizing a hepatitis B virus (HBV) surface antigen by administration of murabutide associated to a synthetic pre-S HBV peptide conjugated to a toxoid carrier. Biochem Biophys Res Commun 1986;140:557–564.

    Article  PubMed  CAS  Google Scholar 

  40. Olberling F, Morin A, Duclos B, Lang JM, Berchey EH, Chedid L. Enhancement of antibody response to a natural fragment of streptococcal M protein by Murabutide administered to healthy volunteers. Int J Immunol 1983;7:398.

    Article  Google Scholar 

  41. Telzak E, Wolff SM, Dinarello CA, et al. Clinical evaluation of the immunoadjuvant murabutide, a derivative of MDP, administered with a tetanus toxoid vaccine. J Infect Dis 1986;153:628–633.

    PubMed  CAS  Google Scholar 

  42. Vidal VF, Casteran N, Riendeau CJ, et al. Macrophage stimulation with Murabutide, an HIV-suppressive muramyl peptide derivative, selectively activates extracellular signal-regulated kinases 1 and 2, C/EBP-β and STAT1: role of CD14 and Toll-like receptors 2 and 4. Eur J Immunol 2001;31:1962–1971.

    Article  PubMed  CAS  Google Scholar 

  43. Vidal V, Dewulf J, Bahr GM. Enhanced maturation and functional capacity of monocyte-derived immature dendritic cells by the synthetic immunomodulator Murabutide. Immunology 2001;103:479–487.

    Article  PubMed  CAS  Google Scholar 

  44. Medzhitov R. Toll-like receptors and innate immunity. Nature Rev Immunol 2001;1:135–145.

    Article  CAS  Google Scholar 

  45. Yang S, Tamai R, Akashi S, et al. Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture. Infect Immun 2001;69:2045–2053.

    Article  PubMed  CAS  Google Scholar 

  46. Bahr GM, Pouillart PR, Chedid LA. Enhancement in vivo of the antiinflammatory and antitumor activities of type I interferon by association with the synthetic immunomodulator murabutide. J Interferon Cytokine Res 1996;16:297–306.

    PubMed  CAS  Google Scholar 

  47. Auci DL, Carucci JA, Chice SM, Smith MC, Dukor P, Durkin HG. Control of IgE responses. 4. Isotype-specific suppression of peak BPO-specific IgE antibody-forming cell responses and of BPO-specific IgE in serum by muramyldipeptide or murabutide after administration to mice by gavage. Int Arch Allergy Immunol 1993;101:167–176.

    Article  PubMed  CAS  Google Scholar 

  48. Bahr GM, Darcissac E, Pouillart PR, Chedid LA. Synergistic effects between recombinant interleukin-2 and the synthetic immunomodulator murabutide: selective enhancement of cytokine release and potentiation of antitumor activity. J Interferon Cytokine Res 1996;16:169–178.

    Article  PubMed  CAS  Google Scholar 

  49. Pouillart PR, Audibert FM, Chedid LA, Lefrancier PL, Bahr GM. Enhancement by muramyl peptides of the protective response of interferon-alpha/beta against encephalomyocarditis virus infection. Int J Immunopharmacol 1996;18:183–192.

    Article  PubMed  CAS  Google Scholar 

  50. Darcissac EC, Truong MJ, Dewulf J, Mouton Y, Capron A, Bahr GM. The synthetic immunomodulator murabutide controls human immunodeficiency virus type 1 replication at multiple levels in macrophages and dendritic cells. J Virol 2000;74:7794–7802.

    Article  PubMed  CAS  Google Scholar 

  51. Bahr GM, Darcissac EC, Casteran N, et al. Selective regulation of human immunodeficiency virus-infected CD4+ lymphocytes by a synthetic immunomodulator leads to potent virus suppression in vitro and in hu-PBL-SCID mice. J Virol 2001;75:6941–6952.

    Article  PubMed  CAS  Google Scholar 

  52. Goasduff T, Darcissac ECA, Vidal V, Capron A, Bahr GM. The transcriptional response of human macrophages to murabutide reflects a spectrum of biological effects for the synthetic immunomodulator. Clin Exp Immunol 2002;128:474–482.

    Article  PubMed  CAS  Google Scholar 

  53. Billaut-Mulot O, Cocude C, Kolesnitchenko V, et al. SS-56, a novel cellular target of autoantibody responses in Sjogren syndrome and systemic lupus erythematosus. J Clin Invest 2001;108:861–869.

    Article  PubMed  CAS  Google Scholar 

  54. Cocude C, Truong MJ, Billaut-Mulot O, et al. A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication. J Virol 2003;84:3215–3225.

    Article  CAS  Google Scholar 

  55. Darcissac EC, Vidal V, Guillaume M, Thebault JJ, Bahr GM. Clinical tolerance and profile of cytokine induction in healthy volunteers following the simultaneous administration of ifn-alpha and the synthetic immunomodulator murabutide. J Interferon Cytokine Res 2001;21:655–661.

    Article  PubMed  CAS  Google Scholar 

  56. Amiel C, de la Tribonniere X, Vidal V, Darcissac E, Mouton Y, Bahr GM. Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator Murabutide in HIV-1-Infected Patients. JAIDS 2002;30:294–305.

    PubMed  CAS  Google Scholar 

  57. De la Tribonniere X, Mouton Y, Vidal V, et al. A phase I study of a six-week cycle of immunotherapy with Murabutide in HIV-1 patients naive to antiretrovirals. Med Sci Monit 2003;9:143–150.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Bahr, G.M. (2006). Immune and Antiviral Effects of the Synthetic Immunomodulator Murabutide. In: Hackett, C.J., Harn, D.A. (eds) Vaccine Adjuvants. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-59259-970-7_10

Download citation

Publish with us

Policies and ethics