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. 1994 Apr;62(4):1137–1143. doi: 10.1128/iai.62.4.1137-1143.1994

Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06.

G B Pier 1, N L Koles 1, G Meluleni 1, K Hatano 1, M Pollack 1
PMCID: PMC186240  PMID: 8132318

Abstract

Structural and antigenic heterogeneity has been noted among lipopolysaccharides (LPS) produced by Pseudomonas aeruginosa within serogroups previously considered to be serologically homogeneous. We characterized murine monoclonal antibodies (MAbs) and immunization-induced human polyclonal antibodies reactive with one or more of five structurally variant LPS subtypes belonging to serogroup 06 of the International Antigenic Typing System. Analyses of five different MAbs employing purified LPS or whole patterns of subtype specificity, ranging from recognition of a single subtype to reactivity with all five. MAb-mediated opsonophagocytic killing and in vivo protection against live challenge in mice correlated, in general, with differential binding to various LPS subtypes. In comparison, sera from human vaccinees immunized with LPS-derived high-molecular-weight polysaccharide from P. aeruginosa Fisher immunotype 1, one of five serogroup 06 subtypes, exhibited LPS binding and opsonic activity against all five subtypes. Antibodies in the human sera effectively inhibited binding to all five LPS subtype antigens of the cross-reactive MAb, LC3-2H2, suggesting the existence of a common serogroup-related epitope. These findings emphasize the importance of defining subtype-associated variations in LPS antigenicity and corresponding differences in antibody specificity and function as a basis for designing immunoprophylactic or therapeutic strategies which target P. aeruginosa LPS.

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Selected References

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  1. Ames P., DesJardins D., Pier G. B. Opsonophagocytic killing activity of rabbit antibody to Pseudomonas aeruginosa mucoid exopolysaccharide. Infect Immun. 1985 Aug;49(2):281–285. doi: 10.1128/iai.49.2.281-285.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cryz S. J., Jr, Fürer E., Germanier R. Passive protection against Pseudomonas aeruginosa infection in an experimental leukopenic mouse model. Infect Immun. 1983 May;40(2):659–664. doi: 10.1128/iai.40.2.659-664.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cryz S. J., Jr, Fürer E., Germanier R. Protection against fatal Pseudomonas aeruginosa burn wound sepsis by immunization with lipopolysaccharide and high-molecular-weight polysaccharide. Infect Immun. 1984 Mar;43(3):795–799. doi: 10.1128/iai.43.3.795-799.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cryz S. J., Jr, Fürer E., Que J. U., Sadoff J. C., Brenner M., Schaad U. B. Clinical evaluation of an octavalent Pseudomonas aeruginosa conjugate vaccine in plasma donors and in bone marrow transplant and cystic fibrosis patients. Antibiot Chemother (1971) 1991;44:157–162. doi: 10.1159/000420310. [DOI] [PubMed] [Google Scholar]
  5. Cryz S. J., Jr, Fürer E., Que J. U. Synthesis and characterization of a Pseudomonas aeruginosa alginate-toxin A conjugate vaccine. Infect Immun. 1991 Jan;59(1):45–50. doi: 10.1128/iai.59.1.45-50.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cryz S. J., Jr, Fürer E., Sadoff J. C., Fredeking T., Que J. U., Cross A. S. Production and characterization of a human hyperimmune intravenous immunoglobulin against Pseudomonas aeruginosa and Klebsiella species. J Infect Dis. 1991 May;163(5):1055–1061. doi: 10.1093/infdis/163.5.1055. [DOI] [PubMed] [Google Scholar]
  7. Cryz S. J., Jr, Sadoff J. C., Fürer E. Octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Microb Pathog. 1989 Jan;6(1):75–80. doi: 10.1016/0882-4010(89)90010-7. [DOI] [PubMed] [Google Scholar]
  8. Cryz S. J., Jr, Sadoff J. C., Que J. U. Conjugate vaccines against Pseudomonas aeruginosa and malaria. Contrib Microbiol Immunol. 1989;10:166–189. [PubMed] [Google Scholar]
  9. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  10. Hector R. F., Collins M. S., Pennington J. E. Treatment of experimental Pseudomonas aeruginosa pneumonia with a human IgM monoclonal antibody. J Infect Dis. 1989 Sep;160(3):483–489. doi: 10.1093/infdis/160.3.483. [DOI] [PubMed] [Google Scholar]
  11. Jones R. J., Roe E. A., Gupta J. L. Controlled trial of Pseudomonas immunoglobulin and vaccine in burn patients. Lancet. 1980 Dec 13;2(8207):1263–1265. doi: 10.1016/s0140-6736(80)92334-x. [DOI] [PubMed] [Google Scholar]
  12. Jones R. J., Roe E. A., Gupta J. L. Controlled trials of a polyvalent pseudomonas vaccine in burns. Lancet. 1979 Nov 10;2(8150):977–982. doi: 10.1016/s0140-6736(79)92559-5. [DOI] [PubMed] [Google Scholar]
  13. Knirel YuA, Vinogradov E. V., Kocharova N. A., Paramonov N. A., Kochetkov N. K., Dmitriev B. A., Stanislavsky E. S., Lányi B. The structure of O-specific polysaccharides and serological classification of Pseudomonas aeruginosa (a review). Acta Microbiol Hung. 1988;35(1):3–24. [PubMed] [Google Scholar]
  14. Knirel Y. A. Polysaccharide antigens of Pseudomonas aeruginosa. Crit Rev Microbiol. 1990;17(4):273–304. doi: 10.3109/10408419009105729. [DOI] [PubMed] [Google Scholar]
  15. Knirel Y. A., Vinogradov E. V., Shashkov A. S., Dmitriev B. A., Kochetkov N. K., Stanislavsky E. S., Mashilova G. M. Somatic antigens of Pseudomonas aeruginosa. The structure of the O-specific polysaccharide chains of lipopolysaccharides of P. aeruginosa serogroup O4 (Lányi) and related serotype O6 (Habs) and immunotype 1 (Fisher). Eur J Biochem. 1985 Aug 1;150(3):541–550. doi: 10.1111/j.1432-1033.1985.tb09055.x. [DOI] [PubMed] [Google Scholar]
  16. Kropinski A. M., Chan L. C., Milazzo F. H. The extraction and analysis of lipopolysaccharides from Pseudomonas aeruginosa strain PAO, and three rough mutants. Can J Microbiol. 1979 Mar;25(3):390–398. doi: 10.1139/m79-060. [DOI] [PubMed] [Google Scholar]
  17. Lam J. S., Handelsman M. Y., Chivers T. R., MacDonald L. A. Monoclonal antibodies as probes to examine serotype-specific and cross-reactive epitopes of lipopolysaccharides from serotypes O2, O5, and O16 of Pseudomonas aeruginosa. J Bacteriol. 1992 Apr;174(7):2178–2184. doi: 10.1128/jb.174.7.2178-2184.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lightfoot J., Lam J. S. Molecular cloning of genes involved with expression of A-band lipopolysaccharide, an antigenically conserved form, in Pseudomonas aeruginosa. J Bacteriol. 1991 Sep;173(18):5624–5630. doi: 10.1128/jb.173.18.5624-5630.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liu P. V., Wang S. Three new major somatic antigens of Pseudomonas aeruginosa. J Clin Microbiol. 1990 May;28(5):922–925. doi: 10.1128/jcm.28.5.922-925.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pennington J. E. Pseudomonas aeruginosa immunotherapy. Eur J Clin Microbiol Infect Dis. 1990 Jun;9(6):377–380. doi: 10.1007/BF01979465. [DOI] [PubMed] [Google Scholar]
  21. Pennington J. E. Pseudomonas aeruginosa. Vaccines and immunotherapy. Infect Dis Clin North Am. 1990 Jun;4(2):259–270. [PubMed] [Google Scholar]
  22. Pier G. B., Bennett S. E. Structural analysis and immunogenicity of Pseudomonas aeruginosa immunotype 2 high molecular weight polysaccharide. J Clin Invest. 1986 Feb;77(2):491–495. doi: 10.1172/JCI112328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pier G. B., Cohen M., Jennings H. Further purification and characterization of high-molecular-weight polysaccharide from Pseudomonas aeruginosa. Infect Immun. 1983 Dec;42(3):936–941. doi: 10.1128/iai.42.3.936-941.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pier G. B. Cross-protection by Pseudomonas aeruginosa polysaccharides. Infect Immun. 1982 Dec;38(3):1117–1122. doi: 10.1128/iai.38.3.1117-1122.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pier G. B., Pollack M. Isolation, structure, and immunogenicity of Pseudomonas aeruginosa immunotype 4 high-molecular-weight polysaccharide. Infect Immun. 1989 Feb;57(2):426–431. doi: 10.1128/iai.57.2.426-431.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pier G. B. Polysaccharide antigens of Pseudomonas aeruginosa. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S337–S340. doi: 10.1093/cid/10.supplement_2.s337. [DOI] [PubMed] [Google Scholar]
  27. Pier G. B. Safety and immunogenicity of high molecular weight polysaccharide vaccine from immunotype 1 Pseudomonas aeruginosa. J Clin Invest. 1982 Feb;69(2):303–308. doi: 10.1172/JCI110453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pier G. B., Sidberry H. F., Sadoff J. C. High-molecular-weight polysaccharide antigen from Pseudomonas aeruginosa immunotype 2. Infect Immun. 1981 Nov;34(2):461–468. doi: 10.1128/iai.34.2.461-468.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pier G. B., Sidberry H. F., Zolyomi S., Sadoff J. C. Isolation and characterization of a high-molecular-weight polysaccharide from the slime of Pseudomonas aeruginosa. Infect Immun. 1978 Dec;22(3):908–918. doi: 10.1128/iai.22.3.908-918.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pier G. B., Thomas D. M. Characterization of the human immune response to a polysaccharide vaccine from Pseudomonas aeruginosa. J Infect Dis. 1983 Aug;148(2):206–213. doi: 10.1093/infdis/148.2.206. [DOI] [PubMed] [Google Scholar]
  31. Pier G. B., Thomas D. M. Lipopolysaccharide and high-molecular-weight polysaccharide serotypes of Pseudomonas aeruginosa. J Infect Dis. 1982 Feb;145(2):217–223. doi: 10.1093/infdis/145.2.217. [DOI] [PubMed] [Google Scholar]
  32. Pollack M., Chia J. K., Koles N. L., Miller M., Guelde G. Specificity and cross-reactivity of monoclonal antibodies reactive with the core and lipid A regions of bacterial lipopolysaccharide. J Infect Dis. 1989 Feb;159(2):168–188. doi: 10.1093/infdis/159.2.168. [DOI] [PubMed] [Google Scholar]
  33. Pollack M., Pier G. B., Prescott R. K. Immunization with Pseudomonas aeruginosa high-molecular-weight polysaccharides prevents death from Pseudomonas burn infections in mice. Infect Immun. 1984 Feb;43(2):759–760. doi: 10.1128/iai.43.2.759-760.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Pollack M., Tao M., Akiyama M., Pier G. B., Koles N. L. In vitro and in vivo functional activities of monoclonal antibodies reactive with Pseudomonas aeruginosa serogroup 6 lipopolysaccharides. Antibiot Chemother (1971) 1991;44:163–171. doi: 10.1159/000420311. [DOI] [PubMed] [Google Scholar]
  35. Pollack M., Young L. S. Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man. J Clin Invest. 1979 Feb;63(2):276–286. doi: 10.1172/JCI109300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rowe P. S., Meadow P. M. Structure of the Core oligosaccharide from the lipopolysaccharide of Pseudomonas aeruginosa PAC1R and its defective mutants. Eur J Biochem. 1983 May 2;132(2):329–337. doi: 10.1111/j.1432-1033.1983.tb07366.x. [DOI] [PubMed] [Google Scholar]
  37. Saravolatz L. D., Markowitz N., Collins M. S., Bogdanoff D., Pennington J. E. Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and nonseptic patients. J Infect Dis. 1991 Oct;164(4):803–806. doi: 10.1093/infdis/164.4.803. [DOI] [PubMed] [Google Scholar]
  38. Schaad U. B., Lang A. B., Wedgwood J., Ruedeberg A., Que J. U., Fürer E., Cryz S. J., Jr Safety and immunogenicity of Pseudomonas aeruginosa conjugate A vaccine in cystic fibrosis. Lancet. 1991 Nov 16;338(8777):1236–1237. doi: 10.1016/0140-6736(91)92103-9. [DOI] [PubMed] [Google Scholar]
  39. Vale T. A., Gaston M. A., Pitt T. L. Subdivision of O serotypes of Pseudomonas aeruginosa with monoclonal antibodies. J Clin Microbiol. 1988 Sep;26(9):1779–1782. doi: 10.1128/jcm.26.9.1779-1782.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Young L. S. Human immunity to Pseudomonas aeruginosa. II. Relationship between heat-stable opsonins and type-specific lipopolysaccharides. J Infect Dis. 1972 Sep;126(3):277–287. doi: 10.1093/infdis/126.3.277. [DOI] [PubMed] [Google Scholar]
  41. Young L. S., Meyer R. D., Armstrong D. Pseudomonas aeruginosa vaccine in cancer patients. Ann Intern Med. 1973 Oct;79(4):518–527. doi: 10.7326/0003-4819-79-4-518. [DOI] [PubMed] [Google Scholar]
  42. Young L. S. Role of antibody in infections due to Pseudomonas aeruginosa. J Infect Dis. 1974 Nov;130 (Suppl)(0):S111–S118. doi: 10.1093/infdis/130.supplement.s111. [DOI] [PubMed] [Google Scholar]
  43. Zweerink H. J., Gammon M. C., Hutchison C. F., Jackson J. J., Pier G. B., Puckett J. M., Sewell T. J., Sigal N. H. X-linked immunodeficient mice as a model for testing the protective efficacy of monoclonal antibodies against Pseudomonas aeruginosa. Infect Immun. 1988 May;56(5):1209–1214. doi: 10.1128/iai.56.5.1209-1214.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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