The Role of Human Monoclonal Antibody Specificity and Avidity in the Protection Against Gram-negative Bacteria

  • U. Bruderer
  • E. Fürer
  • S. J. CryzJr.
  • A. B. Lang
Conference paper

Abstract

Despite the use of increasingly potent antimicrobial drugs, an increase of fatal bacteria infections has been noted (Baumgartner and Glauser 1987, Cryz 1987). This failure of antibiotic treatment urges the search for alternative therapies. The use of passive immunotherapy with human monoclonal antibodies (MAb) is generally accepted as the most promising aproach (Teng et al. 1985, Larrick et al. 1986, Masuho 1988). However, the intricacies of human MAb generation may be responsible for the fact that so little progress has been reported in this field.

Keywords

Hydrolysis Aldehyde Polysaccharide Bacillus Pseudomonas 

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References

  1. Baumgartner JD, Glauser MP (1987) Controversies in the use of passive immunotherapy for bacterial infections in the critically ill patient. Rev Infec D 9: 194–205CrossRefGoogle Scholar
  2. Baumgartner JD, Heumann D, Gerlain J, Weinbreck P, Grau GE, Glauser MP (1990) Association between protective efficacy of antilipopolysaccharide (LPS) antibodies and suppression of LPS-induced tumor necrosis factor a and interleukin 6. Comparison of O side chain-specific antibodies with core LPS antibodies. J Exp Med 171: 889–896PubMedCrossRefGoogle Scholar
  3. Bruderer U, Aebersold R, Blaser K, Heusser CH (1988) Characterization of the Group I and Group II antibodies against PC-KLH in normal and T15 suppressed BALB/c mice. Immunology 64: 385–390PubMedGoogle Scholar
  4. Bruderer U, Stenzel-Poore MP, Bächinger HP, Fellman JH, Rittenberg MB (1989) Antibody combining site heterogeneity within the response to phosphocholine-keyhole limpet hemocyanin. Mol Immunol 26: 63–71PubMedCrossRefGoogle Scholar
  5. Bruderer U, Fürer E, Cryz Jr SL, Lang AB (1990) Differences in the protective capacity of naturally occurring and deliberately induced human anti-Pseudomonas antibodies. Manuscript submittedGoogle Scholar
  6. Collins MS, Roby RE (1984) Protective activity of an intravenous immune globulin (human) enriched in antibody against lipopolysaccharide antigens of Pseudomonas aeruginosa. AMJ Med 76 (3A): 168–174CrossRefGoogle Scholar
  7. Cryz Jr SL, Fürer E, Germanier R (1983) Protection against Pseudomonas aeruginosa infection in a murine burn wound sepsis model by passive transfer of antitoxin A, antielastase, and antilipopolysaccharide. Infect Immun 39: 1072–1079PubMedGoogle Scholar
  8. Cryz Jr SL, Lang AB, Sadoff JC, Germanier R, Fürer E (1987) Vaccine potential of Pseudo- monas aeruginosa O-polysaccharide-toxinA conjugates. Infect Immun 55: 1547–1551PubMedGoogle Scholar
  9. Germanier R, Fürer E (1971) Immunity in experimental salmonellosis II. Basis for the avirulence and protective capacity of gal E mutants of Salmonella typhimurium. Infect Immun 4: 663–673PubMedGoogle Scholar
  10. Greisman SE, Johnston CA (1987) Failure of antisera to J5 and R595 rough mutants to reduce endotoxemic lethality. J Infect Dis 157: 54–64CrossRefGoogle Scholar
  11. Lang AB, Fürer E, Larrick JW, Cryz Jr SL (1989) Isolation and characterization of a human monoclonal antibody that recognizes epitopes shared by Pseudomonas aeruginosa immunotype 1,3,4 and 6 lipopolysaccharides. Infect Immun 57: 3851–3855PubMedGoogle Scholar
  12. Lang AB, Fürer E, Senyk G, Larrick JW, Cryz Jr SL (1990 a) Systematic generation of antigen specific human monoclonal antibodies with therapeutical activities using active immunization. Human Antibodies and Hybridomas 1 (in press)Google Scholar
  13. Lang AB, Bruderer U, Fürer E, LarrickJW, Cryz Jr SL (1990 b) Immunoprotective capacities of human and murine monoclonal antibodies recognizing serotype specific and common determinants of gram-negative bacteria. In: Borrebaeck C, Larrick JW (eds) Therapeutic monoclonal antibodies. Stockton Press, New York (in press)Google Scholar
  14. Larrick JW, Bourla JM (1986) Prospects of the therapeutic use of human monoclonal antibodies. J Biol Response Mod 5: 379–393PubMedGoogle Scholar
  15. Masuho Y (1988) Human monoclonal antibodies: prospects for the use as a passive immunotherapy. Serodiag Immunother Infect Dis 2: 319–340CrossRefGoogle Scholar
  16. Stamm WE, Martin SM, Bennett JV (1977) Epidemiology of nosocomial infections due to gram-negative bacilli: Aspects relevant to development and use of vaccines. J Inf Dis 136: S151 - S160CrossRefGoogle Scholar
  17. Teng NNH, Kaplan HS, Hebert J, Moore C, Douglas H, Wunderlich A, Braude Al (1985) Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc Natl Acad Sci USA 82: 1790–1794PubMedCrossRefGoogle Scholar
  18. Ziegler EJ, McCutchan JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, Braude Al (1982) Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 307: 1225–1230PubMedCrossRefGoogle Scholar
  19. Zinner SH, McCabe WR (1976) Effects of IgM and IgG antibody in patients with bacteremia due to gram-negative bacilli. J Infect Dis 133: 37–45PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • U. Bruderer
    • 1
  • E. Fürer
    • 1
  • S. J. CryzJr.
    • 1
  • A. B. Lang
    • 1
  1. 1.Swiss Serum & Vaccine InstituteBerneSwitzerland

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