Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Sep;62(9):3608–3616. doi: 10.1128/iai.62.9.3608-3616.1994

Immunogenic and antigenic properties of a heptavalent high-molecular-weight O-polysaccharide vaccine derived from Pseudomonas aeruginosa.

K Hatano 1, S Boisot 1, D DesJardins 1, D C Wright 1, J Brisker 1, G B Pier 1
PMCID: PMC303009  PMID: 7520416

Abstract

We investigated the chemical and immunologic properties of a heptavalent vaccine composed of high-molecular-weight polymers of the lipopolysaccharide (LPS) O polysaccharides representative of the most common clinical isolates of Pseudomonas aeruginosa. We also evaluated the serum antibody response to nonvaccine strains of P. aeruginosa, including strains expressing structural variants (subtype strains) of the O side chain of the vaccine strains. The polyvalent vaccine, prepared under conditions suitable for human use, contained low levels of contaminants and passed preclinical safety and toxicity tests required for human use. Chemical analyses indicated that individual polysaccharides were composed of both O-side chain and core sugars. Following immunization of C3H/HeN mice and New Zealand White rabbits, antibody titers against vaccine components increased between 32- and 200-fold. Antibodies reactive with LPS isolated from smooth and rough nonvaccine strains were also elicited. Analysis of the opsonic activity against the known LPS subtype variants of the vaccine strains revealed a variable pattern of killing, which ranged from opsonic killing of > or = 69% of bacterial cells representing all subtype variants within a serogroup to opsonization of only a minority of the subtype variant strains. Mouse and rabbit immune sera showed different patterns of opsonic activity against subtype strains, indicating that different epitopes on these antigens are immunodominant in the representatives of these two animal species tested. The polyvalent vaccine was effective at eliciting antibodies to vaccine components in mice and rabbits, but it remains to be determined if the current heptavalent formulation contains sufficient components to provoke human antibodies reactive with a majority of clinical strains of P. aeruginosa.

Full text

PDF
3608

Selected References

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

  1. Andrews P. Estimation of molecular size and molecular weights of biological compounds by gel filtration. Methods Biochem Anal. 1970;18:1–53. [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., 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]
  6. 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]
  7. 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]
  8. 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]
  9. Gottlieb D. J., Cryz S. J., Jr, Furer E., Que J. U., Prentice H. G., Duncombe A. S., Brenner M. K. Immunity against Pseudomonas aeruginosa adoptively transferred to bone marrow transplant recipients. Blood. 1990 Dec 15;76(12):2470–2475. [PubMed] [Google Scholar]
  10. Hatano K., Goldberg J. B., Pier G. B. Pseudomonas aeruginosa lipopolysaccharide: evidence that the O side chains and common antigens are on the same molecule. J Bacteriol. 1993 Aug;175(16):5117–5128. doi: 10.1128/jb.175.16.5117-5128.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jarvis W. R., Martone W. J. Predominant pathogens in hospital infections. J Antimicrob Chemother. 1992 Apr;29 (Suppl A):19–24. doi: 10.1093/jac/29.suppl_a.19. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Jones R. J., Roe E. A., Gupta J. L. Low mortality in burned patients in a Pseudomonas vaccine trial. Lancet. 1978 Aug 19;2(8086):401–403. doi: 10.1016/s0140-6736(78)91868-8. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Knirel Y. A. Polysaccharide antigens of Pseudomonas aeruginosa. Crit Rev Microbiol. 1990;17(4):273–304. doi: 10.3109/10408419009105729. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Kuzio J., Kropinski A. M. O-antigen conversion in Pseudomonas aeruginosa PAO1 by bacteriophage D3. J Bacteriol. 1983 Jul;155(1):203–212. doi: 10.1128/jb.155.1.203-212.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Markham R. B., Pier G. B. Immunologic basis for mouse protection provided by high-molecular-weight polysaccharide from immunotype 1 Pseudomonas aeruginosa. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S957–S962. doi: 10.1093/clinids/5.supplement_5.s957. [DOI] [PubMed] [Google Scholar]
  21. Miler J. M., Spilsbury J. F., Jones R. J., Roe E. A., Lowbury E. J. A new polyvalent Pseudomonas vaccine. J Med Microbiol. 1977 Feb;10(1):19–27. doi: 10.1099/00222615-10-1-19. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Pennington J. E. Pseudomonas aeruginosa. Vaccines and immunotherapy. Infect Dis Clin North Am. 1990 Jun;4(2):259–270. [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Pier G. B. Immunochemistry of Pseudomonas aeruginosa lipopolysaccharides and high-molecular-weight polysaccharides. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S950–S956. doi: 10.1093/clinids/5.supplement_5.s950. [DOI] [PubMed] [Google Scholar]
  27. Pier G. B., Koles N. L., Meluleni G., Hatano K., Pollack M. Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06. Infect Immun. 1994 Apr;62(4):1137–1143. doi: 10.1128/iai.62.4.1137-1143.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pier G. B., Pollack M., Cohen M. Immunochemical characterization of high-molecular-weight polysaccharide from Fisher immunotype 3 Pseudomonas aeruginosa. Infect Immun. 1984 Aug;45(2):309–313. doi: 10.1128/iai.45.2.309-313.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Pier G. B. Pseudomonas aeruginosa surface polysaccharide vaccines. New therapeutic approaches from basic research. Antibiot Chemother (1971) 1985;36:157–167. [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Pier G. B., Sidberry H. F., Sadoff J. C. Protective immunity induced in mice by immunization with high-molecular-weight polysaccharide from Pseudomonas aeruginosa. Infect Immun. 1978 Dec;22(3):919–925. doi: 10.1128/iai.22.3.919-925.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. 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]
  37. Pier G. B., Thomas D., Small G., Siadak A., Zweerink H. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide. Infect Immun. 1989 Jan;57(1):174–179. doi: 10.1128/iai.57.1.174-179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Powderly W. G., Pier G. B., Markham R. B. T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice. J Clin Invest. 1986 Aug;78(2):375–380. doi: 10.1172/JCI112587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Roe E. A., Jones R. J. Immunization of burned patients against Pseudomonas aeruginosa infection at Safdarjang Hospital, New Delhi. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S922–S930. doi: 10.1093/clinids/5.supplement_5.s922. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Wesley J., Fisher A., Fisher M. W. Immunization against Pseudomonas in infection after thermal injury. J Infect Dis. 1974 Nov;130 (Suppl)(0):S152–S158. doi: 10.1093/infdis/130.supplement.s152. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. Young L. S., Yu B. H., Armstrong D. Agar-Gel Precipitating Antibody in Pseudomonas aeruginosa Infections. Infect Immun. 1970 Oct;2(4):495–503. doi: 10.1128/iai.2.4.495-503.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES