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. 1997 May;65(5):1754–1760. doi: 10.1128/iai.65.5.1754-1760.1997

Protective effect of antilipopolysaccharide monoclonal antibody in experimental Klebsiella infection.

T Rukavina 1, B Tícac 1, M Susa 1, N Jendrike 1, S Jonjíc 1, P Lucin 1, R Marre 1, M Doríc 1, M Trautmann 1
PMCID: PMC175211  PMID: 9125558

Abstract

An O-antigen-specific murine monoclonal antibody (MAb) directed against an immunodominant epitope expressed on Klebsiella O1, O6, and O8 lipopolysaccharides (LPS) was examined with respect to its binding to nonencapsulated and encapsulated bacterial cells and its ability to protect against lethal murine Klebsiella sepsis. While the MAb (clone Ru-O1, mouse immunoglobulin G2b) bound well to nonencapsulated organisms of the O1 serogroup, binding was significantly, but not completely, abolished by the presence of the K2 capsule. In a model of experimental Klebsiella peritonitis and sepsis induced by a virulent O1:K2 serogroup strain, higher doses of anti-LPS MAb Ru-O1 than of a previously described anticapsular MAb specific for the K2 capsular polysaccharide were needed to provide protection. However, high-dose (40 microg/g of body weight) pretreatment with anti-LPS MAb Ru-O1 significantly reduced bacterial dissemination to various organs as well as macroscopic and histologic pulmonary alterations. Thus, since the number of Klebsiella capsular antigens occurring in clinical material is too large to be completely "covered" by a K-antigen-specific hyperimmunoglobulin preparation, O-antigen-specific antibodies may supplement K-antigen-specific immunoprophylaxis and -therapy of clinical Klebsiella infection.

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Selected References

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  1. Albertí S., Hernández-Allés S., Gil J., Reina J., Martínez-Beltrán J., Camprubí S., Tomás J. M., Benedí V. J. Development of an enzyme-linked immunosorbent assay method for typing and quantitation of Klebsiella pneumoniae lipopolysaccharide: application to serotype O1. J Clin Microbiol. 1993 May;31(5):1379–1381. doi: 10.1128/jcm.31.5.1379-1381.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BAER H., EHRENWORTH L. The pathogenicity of Klebsiella pneumoniae for mice: the relationship to the quantity and rate of production of type-specific capsular polysaccharide. J Bacteriol. 1956 Nov;72(5):713–717. doi: 10.1128/jb.72.5.713-717.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bryan C. S., Reynolds K. L., Brenner E. R. Analysis of 1,186 episodes of gram-negative bacteremia in non-university hospitals: the effects of antimicrobial therapy. Rev Infect Dis. 1983 Jul-Aug;5(4):629–638. doi: 10.1093/clinids/5.4.629. [DOI] [PubMed] [Google Scholar]
  4. Carpenter J. L. Klebsiella pulmonary infections: occurrence at one medical center and review. Rev Infect Dis. 1990 Jul-Aug;12(4):672–682. doi: 10.1093/clinids/12.4.672. [DOI] [PubMed] [Google Scholar]
  5. Chedid L., Parant M., Parant F., Boyer F. A proposed mechanism for natural immunity to enterobacterial pathogens. J Immunol. 1968 Feb;100(2):292–306. [PubMed] [Google Scholar]
  6. Collins M. S., Roby R. E. Protective activity of an intravenous immune globulin (human) enriched in antibody against lipopolysaccharide antigens of Pseudomonas aeruginosa. Am J Med. 1984 Mar 30;76(3A):168–174. doi: 10.1016/0002-9343(84)90337-1. [DOI] [PubMed] [Google Scholar]
  7. Cross A. S. Intravenous immunoglobins (IVIGs) to prevent and treat infectious diseases. Adv Exp Med Biol. 1995;383:123–130. doi: 10.1007/978-1-4615-1891-4_15. [DOI] [PubMed] [Google Scholar]
  8. Cross A., Artenstein A., Que J., Fredeking T., Furer E., Sadoff J. C., Cryz S. J., Jr Safety and immunogenicity of a polyvalent Escherichia coli vaccine in human volunteers. J Infect Dis. 1994 Oct;170(4):834–840. doi: 10.1093/infdis/170.4.834. [DOI] [PubMed] [Google Scholar]
  9. Cryz S. J., Jr, Cross A. S., Fürer E., Chariatte N., Sadoff J. C., Germanier R. Activity of intravenous immune globulins against Klebsiella. J Lab Clin Med. 1986 Sep;108(3):182–189. [PubMed] [Google Scholar]
  10. Donta S. T., Peduzzi P., Cross A. S., Sadoff J., Haakenson C., Cryz S. J., Jr, Kauffman C., Bradley S., Gafford G., Elliston D. Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group. J Infect Dis. 1996 Sep;174(3):537–543. doi: 10.1093/infdis/174.3.537. [DOI] [PubMed] [Google Scholar]
  11. Edelman R., Taylor D. N., Wasserman S. S., McClain J. B., Cross A. S., Sadoff J. C., Que J. U., Cryz S. J. Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously. Vaccine. 1994 Nov;12(14):1288–1294. doi: 10.1016/s0264-410x(94)80054-4. [DOI] [PubMed] [Google Scholar]
  12. Frasa H., Benaissa-Trouw B., Tavares L., van Kessel K., Poppelier M., Kraaijeveld K., Verhoef J. Enhanced protection by use of a combination of anticapsule and antilipopolysaccharide monoclonal antibodies against lethal Escherichia coli O18K5 infection of mice. Infect Immun. 1996 Mar;64(3):775–781. doi: 10.1128/iai.64.3.775-781.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fujita S., Matsubara F. Latex agglutination text for O serogrouping of Klebsiella species. Microbiol Immunol. 1984;28(6):731–734. doi: 10.1111/j.1348-0421.1984.tb00728.x. [DOI] [PubMed] [Google Scholar]
  14. Held T. K., Trautmann M., Mielke M. E., Neudeck H., Cryz S. J., Jr, Cross A. S. Monoclonal antibody against Klebsiella capsular polysaccharide reduces severity and hematogenic spread of experimental Klebsiella pneumoniae pneumonia. Infect Immun. 1992 May;60(5):1771–1778. doi: 10.1128/iai.60.5.1771-1778.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jarvis W. R., Munn V. P., Highsmith A. K., Culver D. H., Hughes J. M. The epidemiology of nosocomial infections caused by Klebsiella pneumoniae. Infect Control. 1985 Feb;6(2):68–74. doi: 10.1017/s0195941700062639. [DOI] [PubMed] [Google Scholar]
  16. Kelly R. F., Severn W. B., Richards J. C., Perry M. B., MacLean L. L., Tomás J. M., Merino S., Whitfield C. Structural variation in the O-specific polysaccharides of Klebsiella pneumoniae serotype O1 and O8 lipopolysaccharide: evidence for clonal diversity in rfb genes. Mol Microbiol. 1993 Nov;10(3):615–625. doi: 10.1111/j.1365-2958.1993.tb00933.x. [DOI] [PubMed] [Google Scholar]
  17. Kelly R. F., Whitfield C. Clonally diverse rfb gene clusters are involved in expression of a family of related D-galactan O antigens in Klebsiella species. J Bacteriol. 1996 Sep;178(17):5205–5214. doi: 10.1128/jb.178.17.5205-5214.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kim K. S., Kang J. H., Cross A. S., Kaufman B., Zollinger W., Sadoff J. Functional activities of monoclonal antibodies to the O side chain of Escherichia coli lipopolysaccharides in vitro and in vivo. J Infect Dis. 1988 Jan;157(1):47–53. doi: 10.1093/infdis/157.1.47. [DOI] [PubMed] [Google Scholar]
  19. Lang A. B., Bruderer U., Senyk G., Pitt T. L., Larrick J. W., Cryz S. J., Jr Human monoclonal antibodies specific for capsular polysaccharides of Klebsiella recognize clusters of multiple serotypes. J Immunol. 1991 May 1;146(9):3160–3164. [PubMed] [Google Scholar]
  20. Meno Y., Amako K. Morphological evidence for penetration of anti-O antibody through the capsule of Klebsiella pneumoniae. Infect Immun. 1990 May;58(5):1421–1428. doi: 10.1128/iai.58.5.1421-1428.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mizuta K., Ohta M., Mori M., Hasegawa T., Nakashima I., Kato N. Virulence for mice of Klebsiella strains belonging to the O1 group: relationship to their capsular (K) types. Infect Immun. 1983 Apr;40(1):56–61. doi: 10.1128/iai.40.1.56-61.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pennington J. E., Small G. J., Lostrom M. E., Pier G. B. Polyclonal and monoclonal antibody therapy for experimental Pseudomonas aeruginosa pneumonia. Infect Immun. 1986 Oct;54(1):239–244. doi: 10.1128/iai.54.1.239-244.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simoons-Smit A. M., Verweij-van Vught A. M., MacLaren D. M. The role of K antigens as virulence factors in Klebsiella. J Med Microbiol. 1986 Mar;21(2):133–137. doi: 10.1099/00222615-21-2-133. [DOI] [PubMed] [Google Scholar]
  24. Straus D. C., Atkisson D. L., Garner C. W. Importance of a lipopolysaccharide-containing extracellular toxic complex in infections produced by Klebsiella pneumoniae. Infect Immun. 1985 Dec;50(3):787–795. doi: 10.1128/iai.50.3.787-795.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Straus D. C. Production of an extracellular toxic complex by various strains of Klebsiella pneumoniae. Infect Immun. 1987 Jan;55(1):44–48. doi: 10.1128/iai.55.1.44-48.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tomas J. M., Camprubi S., Williams P. Surface exposure of the O-antigen in Klebsiella pneumoniae O1:K1 serotype strains. Microb Pathog. 1988 Aug;5(2):141–147. doi: 10.1016/0882-4010(88)90016-2. [DOI] [PubMed] [Google Scholar]
  27. Tomás J. M., Camprubi S., Merino S., Davey M. R., Williams P. Surface exposure of O1 serotype lipopolysaccharide in Klebsiella pneumoniae strains expressing different K antigens. Infect Immun. 1991 Jun;59(6):2006–2011. doi: 10.1128/iai.59.6.2006-2011.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Trautmann M., Cross A. S., Reich G., Held H., Podschun R., Marre R. Evaluation of a competitive ELISA method for the determination of Klebsiella O antigens. J Med Microbiol. 1996 Jan;44(1):44–51. doi: 10.1099/00222615-44-1-44. [DOI] [PubMed] [Google Scholar]
  29. Trautmann M., Cryz S. J., Jr, Sadoff J. C., Cross A. S. A murine monoclonal antibody against Klebsiella capsular polysaccharide is opsonic in vitro and protects against experimental Klebsiella pneumoniae infection. Microb Pathog. 1988 Sep;5(3):177–187. doi: 10.1016/0882-4010(88)90020-4. [DOI] [PubMed] [Google Scholar]
  30. Trautmann M., Vogt K., Hammack C., Cross A. S. A murine monoclonal antibody defines a unique epitope shared by Klebsiella lipopolysaccharides. Infect Immun. 1994 Apr;62(4):1282–1288. doi: 10.1128/iai.62.4.1282-1288.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Williams P., Lambert P. A., Brown M. R., Jones R. J. The role of the O and K antigens in determining the resistance of Klebsiella aerogenes to serum killing and phagocytosis. J Gen Microbiol. 1983 Jul;129(7):2181–2191. doi: 10.1099/00221287-129-7-2181. [DOI] [PubMed] [Google Scholar]

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