Skip to main content

Advertisement

Log in

Use of Bacterial Ribosomal Immunostimulators in Respiratory Tract Infections

  • Treatment Review
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Bacterial ribosomes, composed of proteins and RNA, have been used for nearly 30 years as immunostimulators. Preparations from about 30 different species of bacteria, as well as from fungi or parasites, have been used. Ribosomes have been tested in a number of animal models, and demonstrated to induce both specific immunity and protection. Paradoxically, although only a small part of these studies have dealt with micro-organisms involved in respiratory infections, most of the clinical trials involving ribosomes have used preparations obtained from such bacteria. Ribosomal preparations have been shown to reduce and prevent recurrent infections of the upper respiratory tract in humans.

Microbial subcellular fractions induce protective immunity against whole wild-type bacteria, even across serotypic diversities. This observation triggered numerous studies aimed at identifying the immunogenic component of ribosomes. The role of RNA has been ruled out for most species, but it may act as an adjuvant to enhance the immunogenicity of peptide motifs bound to the ribosomes. Finally, although many animal models have used subcutaneous immunisation and intraperitoneal challenge, ribosomal preparations have been shown to be efficient in the more recently explored mucosal routes of vaccination. Oral or intragastric administration of ribosomal preparations actively induces mucosal and protective immune responses against caries or respiratory infections.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Youmans AS, Youmans GP. Immunogenic activity of a ribosomal fraction obtained from Mycobacterium tuberculosis. J Bacteriol 1965; 89: 1291–8

    PubMed  CAS  Google Scholar 

  2. Gregory RL. Microbial ribosomal vaccines. Rev Infect Dis 1986; 8: 208–17

    Article  PubMed  CAS  Google Scholar 

  3. Michalek SM, McGhee JR, Mestecky J, et al. Ingestion of Streptococcus mutans induces secretory IgA and caries immunity. Science 1976; 192: 1238–40

    Article  PubMed  CAS  Google Scholar 

  4. Nikolaeva LV, Savel’ev EP. Molecular-biological and immunological properties of ribosomal vaccines. Biomed Sci 1991; 2: 1–10

    PubMed  CAS  Google Scholar 

  5. Gregory RL, Filler SJ, Michalek SM, et al. Salivary immunoglobulin A and serum antibodies to Streptococcus mutans ribosomal preparations in dental-caries-free and cariessusceptible human subjects. Infect Immun 1986; 51: 348–51

    PubMed  CAS  Google Scholar 

  6. Lieberman MM, Allen RC. Opsonic activity of antisera to ribosomal vaccine fractions with live and formalinized Pseudomonas aeruginosa. Can J Microbiol 1986; 32: 531–3

    Article  PubMed  CAS  Google Scholar 

  7. Lieberman MM, Frank WJ, Brady AV. Protective mechanism of the immune response to a ribosomal vaccine from Pseudomonas aeruginosa. II: In vitro bactericidal and opsonophagocytic studies with specific antiserum. J Surg Res 1988; 44: 251–8

    Article  PubMed  CAS  Google Scholar 

  8. Segal E. Fungal ribosomal vaccines. I: Histoplasma and Candida vaccines. Mycopathologia 1989; 105: 45–8

    Article  PubMed  CAS  Google Scholar 

  9. Millet I, Lafont S, Jeannin M, et al. Proliferative response of human T lymphocytes to a vaccinal preparation of ribosomes from Streptococcus pyogenes. Int Arch Allergy Immunol 1988; 86: 432–5

    Article  CAS  Google Scholar 

  10. Millet I, Lafont S, De Fraissinette A, et al. Polyclonal activation of murine B cells by a membrane proteoglycan of Klebsiella pneumoniae. Clin Exp Immunol 1987; 70: 201–8

    PubMed  CAS  Google Scholar 

  11. Hbabi L, Roques C, Michel G, et al. In vitro stimulation of polymorphonuclear cell adhesion by Ribomunyl and antibiotic + Ribomunyl combinations: effect on CD18, CD35 and CD 16 expression. Int J Immunopharmacol 1993; 15: 163–73

    Article  PubMed  CAS  Google Scholar 

  12. Pujol JL, Klein B, Godard P, et al. Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro. Chest 1991; 100: 644–8

    Article  PubMed  CAS  Google Scholar 

  13. Robert D, Ivanoff B, Fontanges R, et al. Study of the mode of action of ribosomal vaccines from Klebsiella and Streptococcus pneumoniae and their ribonucleic and protein fractions using passive immunization. Microbiol Immunol 1982; 26: 933–40

    PubMed  CAS  Google Scholar 

  14. Tewari RP, Sharma D, Solotorovsky M, et al. Adoptive transfer of immunity from mice immunized with ribosomes of live yeast cells of Histoplasma capsulatum. Infect Immun 1977; 15: 789–95

    PubMed  CAS  Google Scholar 

  15. Field LH, Parker CD, Manclark CR, et al. Evaluation of a ribosomal vaccine against Bordetella pertussis. Infect Immun 1979; 24: 346–51

    PubMed  CAS  Google Scholar 

  16. Levy R, Segal E, Eylan E. Protective immunity against murine candidiasis elicited by Candida albicans ribosomal fractions. Infect Immun 1981; 31: 874–8

    PubMed  CAS  Google Scholar 

  17. Segal E, Nussbaum S, Barr-Nea L. Protection against systemic infections with various Candida species elicited by vaccination with Candida albicans ribosomes. Sabouraudia 1985; 23: 75–85

    Article  Google Scholar 

  18. Lynn M, Tewari RP, Solotorovsky M. Immunoprotective activity of ribosomes from Haemophilus influenzae. Infect Immun 1977; 15: 453–62

    PubMed  CAS  Google Scholar 

  19. Zanin C, Béné MC, Martin F, et al. Compartmentalization of specific B-cells in sheep mucosae associated lymphoid organs. Vet Immunol Immunopathol 1994; 42: 349–56

    Article  PubMed  CAS  Google Scholar 

  20. Fontanges R, Robert D, Content Y, et al. Pouvoir vaccinant de ribosomes extraits de K. pneumoniae, S. pneumoniae, S. pyogenes et H. influenzae et d’un fraction membranaire de K. pneumoniae. Rev Fr Allergol Immunol Clin 1977; 17: 35–81

    Google Scholar 

  21. Riottot MM, Fournier JM, Pillot J. Capsular serotypic specificity of the protection conferred to mice by Klebsiella pneumoniae ribosomal preparations. Infect Immun 1979; 24: 476–82

    PubMed  CAS  Google Scholar 

  22. Riottot MM, Fournier JM. Immunoprotective activity of capsular polysaccharide in Klebsiella pneumoniae ribosomal preparations does not involve ribonucleic acid. Infect Immun 1981; 34: 126–30

    PubMed  CAS  Google Scholar 

  23. Riottot MM, Fournier JM, Jouin H. Direct evidence for the involvement of capsular polysaccharide in the immunoprotective activity of Klebsiella pneumoniae ribosomal preparations. Infect Immun 1981; 31: 71–7

    PubMed  CAS  Google Scholar 

  24. Robert D, Bienvenu P, Lafont S, et al. An attempt to localize the vaccinating power of Klebsiella pneumoniae ribosomal preparations using saccharose-gradient ultracentrifugation. Microbiol Immunol 1982; 26: 941–50

    PubMed  CAS  Google Scholar 

  25. Baker RE, Will WE, Larson CL. Delayed hypersensitivity reactions provoked by ribosomes from acid-fast bacilli. I. Ribosomal isolations, characterization, delayed hypersensitivity and specificity. Infect Immun 1972; 6: 258–65

    PubMed  CAS  Google Scholar 

  26. Tantimavanich S, Nagai S, Nomaguchi H, et al. Immunological properties of ribosomal proteins from Mycobacterium bovis BCG. Infect Immun 1993; 61: 4005–7

    PubMed  CAS  Google Scholar 

  27. Youmans GP, Youmans AS. Factors affecting immunogenic activity of mycobacterial ribosomal and ribonucleic acid preparations. J Bacteriol 1969; 99: 42–50

    PubMed  CAS  Google Scholar 

  28. Thomas DW, Weiss E. Response of mice to injection of ribosomal fraction from group B Neisseria meningitidis. Infect Immun 1972; 6: 355–63

    PubMed  CAS  Google Scholar 

  29. Phillips M, Rimler RB. Protections of chickens by ribosomal vaccines from Pasteurella multocida: dependence on homologous lipolysaccharide. Am J Vet Res 1984; 45: 1785–9

    PubMed  CAS  Google Scholar 

  30. Gonggrijp R, Antonissen AC, van den Bosch JF, et al. Ribonuclease- sensitive ribosomal vaccines. Antonie Van Leeuwenhoek 1984; 50: 763–74

    Article  PubMed  CAS  Google Scholar 

  31. Lieberman MM, Ayala E. Active and passive immunity against Pseudomonas aeruginosa with a ribosomal vaccine and antiserum in C3H/HeJ mice. J Immunol 1983; 131: 1–3

    PubMed  CAS  Google Scholar 

  32. Lieberman MM, Walker HL, Ayala E, et al. Active and passive immunization with Pseudomonas aeruginosa ribosomal vaccines and antisera in the burned rat model. J Surg Res 1986; 40: 138–44

    Article  PubMed  CAS  Google Scholar 

  33. Lieberman MM, Frank WJ. Protective mechanism of the immune response to a ribosomal vaccine from Pseudomonas aeruginosa. I. In vivo protection studies in compromised animal models. J Surg Res 1988; 44: 242–50

    Article  PubMed  CAS  Google Scholar 

  34. Lieberman MM. Pseudomonas aeruginosa ribosomal vaccine: a comparison of the immunogenicity of vaccines from two different serotypes. Antibiot Chemother 1989; 42: 193–202

    PubMed  CAS  Google Scholar 

  35. Winston SH, Berry LJ. Immunity induced by ribosomal extracts from Staphylococcus aureus. J Reticuloendothel Soc 1970; 8: 66–73

    PubMed  CAS  Google Scholar 

  36. Au CC, Eisenstein TK. Nature of the cross-protective antigen in subcellular vaccines of Streptococcus pneumoniae induced by a pneumococcal ribosomal protein fraction. Infect Immun 1981; 31: 160–8

    PubMed  CAS  Google Scholar 

  37. Swendsen CL, Johnson W. Humoral immunity to Streptococcus pneumoniae induced by a pneumococcal ribosomal protein fraction. Infect Immun 1976; 14: 345–54

    PubMed  CAS  Google Scholar 

  38. Thompson HCW, Snyder IS. Protection against pneumococcal infection by a ribosomal preparation. Infect Immun 1971; 3: 16–23

    PubMed  CAS  Google Scholar 

  39. Schalla WO, Johnson W. Immunogenicity of ribosomal vaccines isolated from Group A, type 14 Streptococcus pyogenes. Infect Immun 1975; 11: 132–41

    Google Scholar 

  40. Green BA, Johnson W. Immunogenicity of ribosomes from enzymatically lysed Streptococcus pyogenes. Infect Immun 1980; 27: 424–30

    PubMed  CAS  Google Scholar 

  41. Lynn M, Katz MA, Santucci Jr TF. Naturally occurring antibodies in human sera that react with Haemophilus influenzae type b ribosomal vaccine. J Clin Microbiol 1983; 17: 844–7

    PubMed  CAS  Google Scholar 

  42. Béné MC, Kahl L, Perruchet AM, et al. Bacterial lysates and ribosomes as inducers of specific immune responses: a comparative study. Scand J Immunol 1993; 38: 496–8

    Article  PubMed  Google Scholar 

  43. Blaive B, Demichelis B, Lemoigne F, et al. Efficacité de la vaccination par extraits ribosomaux dans le traitement préventif des episodes infectieux des bronchopathies chroniques. Med Mai Infect 1982; 12: 475–9

    Article  Google Scholar 

  44. Charachon R, Junien Lavillauroy P, Fumex JP. Multicentric study of the effectiveness of ribosomal vaccine (D53) in the prevention of episodes of bacterial infection encountered in ENT pathology. Arzneimittel Forschung 1980; 30: 214–20

    PubMed  CAS  Google Scholar 

  45. Faure GC, Béné MC, Simon C, et al. Increase in specific antibody-forming cells in human tonsils after oral stimulation with D-53, a ribosomal vaccine. Int J Immunopharmacol 1990; 12: 315–20

    Article  PubMed  CAS  Google Scholar 

  46. Faure GC, Hauer S, Molé C, et al. Peripheral blood specific antibody-forming cells after oral stimulation with a ribosomal vaccine. Dev Biol Stand 1992; 77: 175–81

    PubMed  CAS  Google Scholar 

  47. Ferreira N, Palma-Carlos AG. Thymectomie et Ribomunyl: à propos de deux observations. Allerg Immunol (Paris) 1988; 20: 173–80

    CAS  Google Scholar 

  48. Klimek L, Kahl L, Béné MC, et al. Spezifische Plasmazellpopulationen in humanen Gaumentonsillen nach oraler Immunstimulation. Allergologie 1993; 16: 194–7

    Google Scholar 

  49. Menardo JL, Bousquet J, Clavel R, et al. Immunostimulation à visée respiratoire par un vaccin administré par voie orale. Poumon Coeur 1982; 38: 297–300

    PubMed  CAS  Google Scholar 

  50. Michel FB, Dussourd d’Hinterland L, Guerrero AJ, et al. Prévention de l’ infection respiratoire bactérienne par vaccin ribosomal. Nouv Presse Med 1977; 6: 1664

    Google Scholar 

  51. Michel FB, Dussourd D’Hinterland L, Bousquet J, et al. Immunostimulation by a ribosomal vaccine associated with a bacterial extract cell wall adjuvant in humans. Infect Immun 1978; 20: 760–9

    PubMed  CAS  Google Scholar 

  52. Sanchez-Palacios A, Quintero A, Martin Escudero JC, et al. Immunotherapy with standard bacterial and bacterial ribosomal antigens in childhood bronchial asthma. Allergol Immunopathol 1986; 14: 383–91

    CAS  Google Scholar 

  53. Subira ML, Oehling A, Dieguez I, et al. Immunotherapy with bacterial ribosomal antigens in bronchial asthma. II Immunological study. Allergol Immunopathol 1982; 10: 53–60

    CAS  Google Scholar 

  54. Tessier JF, Gachie JP, Bernadou M, et al. L’efficacité de la vaccination antimicrobienne dans la prévention des épisodes infectieux des bronchopathies chroniques (suspension bactérienne, extraits ribosomaux, placebo). Rev Fr Mai Respir 1980; 8: 239–46

    CAS  Google Scholar 

  55. Vautel JM, Cauquil J, Perruchet AM, et al. Prevention of recurrent ear, nose and throat infections in young children with Ribomunyl: double-blind, placebo-controlled study. Curr Ther Res 1993; 53: 722–9

    Article  Google Scholar 

  56. Zanin C, Perrin P, Béné MC, et al. Antibody-producing cells in peripheral blood and tonsils after oral treatment of children with bacterial ribosomes. Int J Immunopharmacol 1994; 16: 497–505

    Article  PubMed  CAS  Google Scholar 

  57. Zanin C, Béné MC, Perruchet AM, et al. Bacterial crude extracts or ribosomes are recognized similarly by peripheral and mucosal B-cells. FEMS Immunol Med Microbiol 1994; 10: 11–8

    Article  PubMed  CAS  Google Scholar 

  58. Dussourd d’Hinterland L, Pinel AM, Rey G. Immunological study. Drug Res 1980; 30: 132–41

    Google Scholar 

  59. Dussourd d’Hinterland L, Normier G, Durand I. Ribosomal vaccines: preparation of subcellular fractions. Arzneimittel Forschung 1980; 30: 126–32

    PubMed  Google Scholar 

  60. Caulfield MP, Horiuchi S, Tai PC, et al. The 64 kilodalton membrane protein of Bacillus subtilis is also present as a multiprotein complex on membrane-free ribosomes. Proc Natl Acad Sci USA 1984; 81: 7772–6

    Article  PubMed  CAS  Google Scholar 

  61. Robert D, Normier G, Lafont S, et al. Role of the polysaccharide and of the lipopolysaccharide in the immunoprotective capacity of Klebsiella pneumoniae ribosomes. Acta Pathol Microbiol Immunol Scand Sect C 1984; 83: 293–9

    Google Scholar 

  62. Kita E, Tsukao N, Kitajima S, et al. Immunogenic dialyzable factor derived from a ribosomal fraction of Salmonella typhimurium. II. Isolation and characterization of the protective moiety in the dialyzable factor. Microbiol Immunol 1983; 27: 117–30

    PubMed  CAS  Google Scholar 

  63. Normier G, Pinel AM, Dussourd d’Hinterland L, et al. Ribosomes as carriers for antigenic determinants of the surface of microorganisms. Dev Biol Stand 1992; 77: 79–85

    PubMed  CAS  Google Scholar 

  64. Janetzki S, Srivastava PK. Heat shock protein peptide complexes as therapeutic vaccines against human cancer. Clin Immunother 1995; 3: 325–9

    Article  Google Scholar 

  65. Gregory RL, Schechmeister IL. Humoral and cell-mediated responses to a ribosomal preparation from Streptococcus mutans. Infect Immun 1982; 38: 1094–101

    PubMed  CAS  Google Scholar 

  66. Lafont S, Millet I, Kouassi E, et al. Induction of murine B cell proliferation and immunoglobulin synthesis by some bacterial ribosomes. Microbiol Immunol 1988; 32: 1043–58

    PubMed  CAS  Google Scholar 

  67. Gregory RL, Michalek SM, Schechmeister IL, et al. Effective immunity to dental caries: protection of gnotobiotic rats by local immunization with a ribosomal preparation from Streptococcus mutans. Microbiol Immunol 1983; 27: 787–800

    PubMed  CAS  Google Scholar 

  68. Gregory RL, Michalek SM, Richardson G, et al. Characterization of immune response to oral administration of Streptococcus sobrinus ribosomal preparations in liposomes. Infect Immun 1986; 54: 780–6

    PubMed  CAS  Google Scholar 

  69. Chernokhvostova EV, Lyubinskaya MM, Belkin ZP, et al. Protective milk O antibodies induced in guinea pigs by parenteral Shigella ribosomal vaccine. Int Arch Allergy Appl Immunol 1990; 92: 265–7

    Article  PubMed  CAS  Google Scholar 

  70. Kraehenbuhl JP, Neutra M. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 1992; 72: 853–79

    PubMed  CAS  Google Scholar 

  71. Banz K, Schwicker D, Thomas AM. Economic evaluation of immunoprophylaxis in children with recurrent ear, nose and throat infections. Pharmacoeconomics 1994; 6: 464–77

    Article  PubMed  CAS  Google Scholar 

  72. Phillips M, Eisenstein TK, Meissler J. Immunomodulation of the antibody response to lipopolysaccharide in C3H/HeJ mice by complexing with heterologous ribosomes. Infect Immun 1985; 48: 244–7

    PubMed  CAS  Google Scholar 

  73. Cabrera-Contreras R, Plescia O, Solotorovsky M, et al. Enhancement of immunogenic activity of ribosomal preparations from Haemophilus influenzae by various adjuvants. Vaccine 1985; 3: 103–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faure, G., Béné, M.C. Use of Bacterial Ribosomal Immunostimulators in Respiratory Tract Infections. Clin Immunother 4, 138–146 (1995). https://doi.org/10.1007/BF03259078

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259078

Keywords

Navigation