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. 1988 Aug;56(8):1873–1879. doi: 10.1128/iai.56.8.1873-1879.1988

Human monoclonal antibodies that protect mice against challenge with Pseudomonas aeruginosa.

H J Zweerink 1, M C Gammon 1, C F Hutchison 1, J J Jackson 1, D Lombardo 1, K M Miner 1, J M Puckett 1, T J Sewell 1, N H Sigal 1
PMCID: PMC259495  PMID: 3135264

Abstract

Lymphocytes from healthy volunteers and from cystic fibrosis patients were transformed with Epstein-Barr virus and cultured at a limiting dilution to generate lymphoblastoid cell lines that secreted human monoclonal antibodies specific for lipopolysaccharide (LPS) from Pseudomonas aeruginosa. Three cell lines (RM5, FDD7, and 11F9) produced immunoglobulin M (IgM) antibody species that reacted specifically with P. aeruginosa Fisher immunotypes 2, 4, and 5, respectively, and with LPS extracted from these immunotypes. A fourth cell line (9H10) produced a single IgM antibody species that recognized P. aeruginosa immunotypes 3, 6, and 7 and LPS extracted from them. Monoclonal antibodies secreted by cell lines RM5, FDD7, and 11F9 protected neutropenic mice prophylactically against challenge with P. aeruginosa immunotypes 2, 4, and 5, and those secreted by 9H10 protected against P. aeruginosa immunotypes 3 and 6 but did not protect against immunotype 7. In vivo experiments indicated that antibodies protected mice against infection by increasing the rate of bacterial clearance.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amsbaugh D. F., Hansen C. T., Prescott B., Stashak P. W., Barthold D. R., Baker P. J. Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. I. Evidence that an X-linked gene plays a decisive role in determining responsiveness. J Exp Med. 1972 Oct 1;136(4):931–949. doi: 10.1084/jem.136.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett J. V. Nosocomial infections due to Pseudomonas. J Infect Dis. 1974 Nov;130 (Suppl)(0):S4–S7. doi: 10.1093/infdis/130.supplement.s4. [DOI] [PubMed] [Google Scholar]
  3. Bodey G. P., Bolivar R., Fainstein V., Jadeja L. Infections caused by Pseudomonas aeruginosa. Rev Infect Dis. 1983 Mar-Apr;5(2):279–313. doi: 10.1093/clinids/5.2.279. [DOI] [PubMed] [Google Scholar]
  4. Briles D. E., Forman C., Hudak S., Claflin J. L. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J Exp Med. 1982 Oct 1;156(4):1177–1185. doi: 10.1084/jem.156.4.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cross A., Allen J. R., Burke J., Ducel G., Harris A., John J., Johnson D., Lew M., MacMillan B., Meers P. Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S837–S845. doi: 10.1093/clinids/5.supplement_5.s837. [DOI] [PubMed] [Google Scholar]
  6. Cryz S. J., Jr, Fürer E., Germanier R. Protection against Pseudomonas aeruginosa infection in a murine burn wound sepsis model by passive transfer of antitoxin A, antielastase, and antilipopolysaccharide. Infect Immun. 1983 Mar;39(3):1072–1079. doi: 10.1128/iai.39.3.1072-1079.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Darveau R. P., Hancock R. E. Procedure for isolation of bacterial lipopolysaccharides from both smooth and rough Pseudomonas aeruginosa and Salmonella typhimurium strains. J Bacteriol. 1983 Aug;155(2):831–838. doi: 10.1128/jb.155.2.831-838.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dmitriev B. A., Knirel Y. A., Kocharova N. A., Kochetkov N. K., Stanislavsky E. S., Mashilova G. M. Somatic antigens of Pseudomonas aeruginosa. The structure of the polysaccharide chain of Ps. aeruginosa O-serogroup 7 (Lanyi) lipopolysacharide. Eur J Biochem. 1980 May;106(2):643–651. doi: 10.1111/j.1432-1033.1980.tb04612.x. [DOI] [PubMed] [Google Scholar]
  10. Dmitriev B. A., Kocharova N. A., Knirel Y. A., Shashkov A. S., Kochetkov N. K., Stanislavsky E. S., Mashilova G. M. Somatic Antigens of Pseudomonas aeruginosa. The structure of the polysaccharide chain of Ps.aeruginosa O:6 (Lanyi) lipopolysaccharide. Eur J Biochem. 1982 Jun 15;125(1):229–237. doi: 10.1111/j.1432-1033.1982.tb06673.x. [DOI] [PubMed] [Google Scholar]
  11. Farmer J. J., 3rd, Weinstein R. A., Zierdt C. H., Brokopp C. D. Hospital outbreaks caused by Pseudomonas aeruginosa: importance of serogroup O11. J Clin Microbiol. 1982 Aug;16(2):266–270. doi: 10.1128/jcm.16.2.266-270.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fisher M. W., Devlin H. B., Gnabasik F. J. New immunotype schema for Pseudomonas aeruginosa based on protective antigens. J Bacteriol. 1969 May;98(2):835–836. doi: 10.1128/jb.98.2.835-836.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Knirel YuA, Vinogradov E. V., Shashkov A. A., Dmitriev B. A., Kochetkov N. K., Stanislavsky E. S., Mashilova G. M. Somatic antigens of Pseudomonas aeruginosa. The structure of O-specific polysaccharide chains of P. aeruginosa O:3(a),c and O:3a,d,e lipopolysaccharides. Eur J Biochem. 1983 Aug 1;134(2):289–297. doi: 10.1111/j.1432-1033.1983.tb07564.x. [DOI] [PubMed] [Google Scholar]
  14. 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 O-specific polysaccharide chains of P. aeruginosa O:3a, b and O:3a, d lipopolysaccharides. Eur J Biochem. 1982 Nov;128(1):81–90. [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 Ps.aeruginosa O:2 (Lanyi) lipopolysaccharides. Eur J Biochem. 1982 Jun 15;125(1):221–227. doi: 10.1111/j.1432-1033.1982.tb06672.x. [DOI] [PubMed] [Google Scholar]
  16. MacIntyre S., Lucken R., Owen P. Smooth lipopolysaccharide is the major protective antigen for mice in the surface extract from IATS serotype 6 contributing to the polyvalent Pseudomonas aeruginosa vaccine PEV. Infect Immun. 1986 Apr;52(1):76–84. doi: 10.1128/iai.52.1.76-84.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McManus A. T., Mason A. D., Jr, McManus W. F., Pruitt B. A., Jr Twenty-five year review of Pseudomonas aeruginosa bacteremia in a burn center. Eur J Clin Microbiol. 1985 Apr;4(2):219–223. doi: 10.1007/BF02013601. [DOI] [PubMed] [Google Scholar]
  18. Moody M. R., Young V. M., Kenton D. M., Vermeulen G. D. Pseudomonas aeruginosa in a center for cancer research. I. Distribution of intraspecies types from human and environmental sources. J Infect Dis. 1972 Feb;125(2):95–101. doi: 10.1093/infdis/125.2.95. [DOI] [PubMed] [Google Scholar]
  19. Morrison A. J., Jr, Wenzel R. P. Epidemiology of infections due to Pseudomonas aeruginosa. Rev Infect Dis. 1984 Sep-Oct;6 (Suppl 3):S627–S642. doi: 10.1093/clinids/6.supplement_3.s627. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Rosenstreich D. L., Weinblatt A. C., O'Brien A. D. Genetic control of resistance to infection in mice. Crit Rev Immunol. 1982 Jun;3(4):263–330. [PubMed] [Google Scholar]
  22. Sawada S., Kawamura T., Masuho Y. Immunoprotective human monoclonal antibodies against five major serotypes of Pseudomonas aeruginosa. J Gen Microbiol. 1987 Dec;133(12):3581–3590. doi: 10.1099/00221287-133-12-3581. [DOI] [PubMed] [Google Scholar]
  23. Sawada S., Kawamura T., Masuho Y., Tomibe K. Characterization of a human monoclonal antibody to lipopolysaccharides of Pseudomonas aeruginosa serotype 5: a possible candidate as an immunotherapeutic agent for infections with P. aeruginosa. J Infect Dis. 1985 Nov;152(5):965–970. doi: 10.1093/infdis/152.5.965. [DOI] [PubMed] [Google Scholar]
  24. Sawada S., Suzuki M., Kawamura T., Fujinaga S., Masuho Y., Tomibe K. Protection against infection with Pseudomonas aeruginosa by passive transfer of monoclonal antibodies to lipopolysaccharides and outer membrane proteins. J Infect Dis. 1984 Oct;150(4):570–576. doi: 10.1093/infdis/150.4.570. [DOI] [PubMed] [Google Scholar]
  25. Scher I. The CBA/N mouse strain: an experimental model illustrating the influence of the X-chromosome on immunity. Adv Immunol. 1982;33:1–71. doi: 10.1016/s0065-2776(08)60834-2. [DOI] [PubMed] [Google Scholar]
  26. Sherertz R. J., Sarubbi F. A. A three-year study of nosocomial infections associated with Pseudomonas aeruginosa. J Clin Microbiol. 1983 Jul;18(1):160–164. doi: 10.1128/jcm.18.1.160-164.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stein L. D., Sigal N. H. Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production. Cell Immunol. 1983 Jul 15;79(2):309–319. doi: 10.1016/0008-8749(83)90073-4. [DOI] [PubMed] [Google Scholar]
  28. Stoll B. J., Pollack M., Young L. S., Koles N., Gascon R., Pier G. B. Functionally active monoclonal antibody that recognizes an epitope on the O side chain of Pseudomonas aeruginosa immunotype-1 lipopolysaccharide. Infect Immun. 1986 Sep;53(3):656–662. doi: 10.1128/iai.53.3.656-662.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Takigami T., Seki M. Serological investigation on hospital and domestic Pseudomonas aeruginosa strains. Jpn J Exp Med. 1975 Jun;45(3):171–181. [PubMed] [Google Scholar]
  30. Wilkinson S. G. Composition and structure of lipopolysaccharides from Pseudomonas aeruginosa. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S941–S949. doi: 10.1093/clinids/5.supplement_5.s941. [DOI] [PubMed] [Google Scholar]
  31. Young L. S., Armstrong D. Human immunity to Pseudomonas aeruginosa. I. In-vitro interaction of bacteria, polymorphonuclear leukocytes, and serum factors. J Infect Dis. 1972 Sep;126(3):257–276. doi: 10.1093/infdis/126.3.257. [DOI] [PubMed] [Google Scholar]
  32. 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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