Vaccines for Pseudomonas aeruginosa

  • Gregory P. Priebe
  • Gerald B. Pier
Part of the Medical Intelligence Unit book series (MIUN)


Pseudomonas aeruginosa causes a wide variety of serious infections, particularly in the critically ill,1,2 the immunocompromised,3,4 and those with cystic fibrosis.5 It also JL causes community-acquired bacterial ulcerative keratitis of the eye, particularly in users of extended-wear contact lenses.6,7 In the setting of nosocomial pneumonia, the isolation of P. aeruginosa has a strikingly high attributable mortality.8 The prevalence and importance of P aeruginosa in human infections, coupled with the intrinsic antibiotic resistance due to the low permeability of the outer membrane 9 and the presence of multiple drug efflux pumps,10 confer a pressing need for effective vaccines. A large variety of antigenic targets and delivery methods have been used in many preclinical studies of P. aeruginosa vaccines, and there has also been a number of actual human trials. The failure to have an effective vaccine at this time point can be attributed to a large number of factors. The overwhelming issues appear to encompass the wide variety of often redundant virulence factors that render ineffective approaches that target a single or even a few bacterial products; the antigenic and immunogenic properties of the major target of protective immunity, the O antigen of the lipopolysaccharide (LPS); the ability of the organism to have both extracellular and intracellular stages; and an incomplete understanding of the variation in production of antigens at different sites of infection and at different times during the infectious process, particularly as manifest by clinical isolates. This review discusses many of the strategies pursued to date in the quest for an effective vaccine for P. aeruginosa. A diagrammatic representation of the bacterium is presented in (Fig. 1) and helps to categorize the various P. aeruginosa antigens that have been used as vaccine targets.


Cystic Fibrosis Pseudomonas Aeruginosa Cystic Fibrosis Transmembrane Conductance Regulator Outer Membrane Protein Protective Efficacy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Richards MJ, Edwards JR, Culver DH et al. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999; 27(5):887–892.PubMedGoogle Scholar
  2. 2.
    Foca M, Jakob K, Whittier S et al. Endemic Pseudomonas aeruginosa infection in a neonatal intensive care unit. N Engl J Med 2000; 343(10):695–700.PubMedGoogle Scholar
  3. 3.
    Elishoov H, Or R, Strauss N et al. Nosocomial colonization, septicemia, and Hickman/Broviac catheter-related infections in bone marrow transplant recipients. A 5-year prospective study. Medicine 1998; 77(2):83–101.PubMedGoogle Scholar
  4. 4.
    Afessa B, Green B. Bacterial pneumonia in hospitalized patients with HIV infection: the Pulmonary Complications, ICU Support, and Prognostic Factors of Hospitalized Patients with HIV (PIP) Study. Chest 2000; 117(4):1017–1022.PubMedGoogle Scholar
  5. 5.
    Parad RB, Gerard CJ, Zurakowski D et al. Pulmonary outcome in cystic fibrosis is influenced primarily by mucoid Pseudomonas aeruginosa infection and immune status and only modestly by genotype. Infect Immun 1999; 67(9):4744–4750.PubMedGoogle Scholar
  6. 6.
    Schein OD, Glynn RJ, Seddon JM et al. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. N Engl J Med 1989; 321:773–778.PubMedGoogle Scholar
  7. 7.
    Poggio EC, Glynn RJ, Schein OD et al. The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. N Engl J Med 1989; 321:779–783.PubMedGoogle Scholar
  8. 8.
    Rello J, Rue M, Jubert P et al. Survival in patients with nosocomial pneumonia: impact of the severity of illness and the etiologic agent. Crit Care Med 1997; 25(11): 1862–1867.PubMedGoogle Scholar
  9. 9.
    Hancock RE, Woodruff WA. Roles of porin and beta-lactamase in beta-lactam resistance of Pseudomonas aeruginosa. Rev Infect Dis 1988; 10(4):770–775.PubMedGoogle Scholar
  10. 10.
    Poole K, Krebes K, McNally C et al. Multiple antibiotic resistance in Pseudomonas aeruginosa: Evidence for involvement of an efflux Operon. J Bacteriol 1993; 175(22):7363–7372.PubMedGoogle Scholar
  11. 11.
    Liu PV. Exotoxins of Pseudomonas aeruginosa I. Factors which influence the production of exotoxin A. J Infect Dis 1973; 128:506–513.PubMedGoogle Scholar
  12. 12.
    Snell K, Holder IA, Leppla SA et al. Role of exotoxin and protease as possible virulence factors in experimental infections with Pseudomonas aeruginosa. Infect Immun 1978; 19:839–845.PubMedGoogle Scholar
  13. 13.
    Barteil PF, Orr TE, Garcia M. The lethal events in experimental Pseudomonas aeruginosa infection of mice. J Infect Dis 1968; 118(2):165–172.Google Scholar
  14. 14.
    Stieritz DD, Holder IA. Experimental studies of the pathogenesis of Pseudomonas aeruginosa infection: Evidence for the in-vivo production of a lethal toxin. J Med Micro 1978; 11 (2): 101–109.Google Scholar
  15. 15.
    Pavlovskis OR, Edman DC, Leppla SH et al. Protection against experimental Pseudomonas aeruginosa infection in mice by active immunization with exotoxin A toxoids. Infect Immun 1981; 32(2):681–689.PubMedGoogle Scholar
  16. 16.
    Cryz SJ, Jr., Furer E, Germanier R. Passive protection against Pseudomonas aeruginosa infection in an experimental leukopenic mouse model. Infect Immun 1983; 40(2):659–664.PubMedGoogle Scholar
  17. 17.
    Cryz SJ, Jr., Furer 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; 39(3):1072–1079.PubMedGoogle Scholar
  18. 18.
    Fattom AI, Sarwar J, Ortiz A et al. A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge. Infect Immun 1996; 64(5):1659–1665.PubMedGoogle Scholar
  19. 19.
    Wretlind B, Pavlovskis OR. The role of proteases and exotoxin A in the pathogenicity of Pseudomonas aeruginosa infections. Scand J Infect Dis Suppl 1981; 29:13–19.PubMedGoogle Scholar
  20. 20.
    Wretlind B, Pavlovskis OR. Pseudomonas aeruginosa elastase and its role in Pseudomonas infections. Rev Infect Dis 1983; 5 Suppl 5:S998–S1004.PubMedGoogle Scholar
  21. 21.
    Blackwood LL, Stone RM, Iglewski BH et al. Evaluation of Pseudomonas aeruginosa exotoxin A and elastase as virulence factors in acute lung infection. Infect Immun 1983; 39(1): 198–201.PubMedGoogle Scholar
  22. 22.
    Matsumoto T, Tateda K, Furuya N et al. Efficacies of alkaline protease, elastase and exotoxin A toxoid vaccines against gutderived Pseudomonas aeruginosa sepsis in mice. J Med Micro 1998; 47(4):303–308.Google Scholar
  23. 23.
    Kawamoto S, Shibano Y, Fukushima J et al. Site-directed mutagenesis of glu-141 and his-223 in Pseudomonas aeruginosa elastase: Catalytic activity, processing, and protective activity of the elastase against Pseudomonas infection. Infect Immun 1993; 61:1400–1405.PubMedGoogle Scholar
  24. 24.
    Sokol PA, Kooi C, Hodges RS et al. Immunization with a Pseudomonas aeruginosa elastase peptide reduces severity of experimental lung infections due to P. aeruginosa or Burkholderia cepacia. J Infect Dis 2000; 181 (5):1682–1692.PubMedGoogle Scholar
  25. 25.
    Rocchetta HL, Burrows LL, Lam JS. Genetics of O-antigen biosynthesis in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 1999; 63(3):523–553.PubMedGoogle Scholar
  26. 26.
    Wilkinson SG. Composition and structure of lipopolysaccharides from Pseudomonas aeruginosa. Rev Infect Dis 1983; 5Supp 5:S94l–S947.Google Scholar
  27. 27.
    Rivera M, Bryan LE, Hancock RE et al. Heterogeneity of lipopolysaccharides from Pseudomonas aeruginosa: Analysis of lipopolysaccharide chain length. J Bacteriol 1988; 170(2):512–521.PubMedGoogle Scholar
  28. 28.
    Sadovskaya I, Brisson JR, Thibault P et al. Structural characterization of the outer core and the O-chain linkage region of lipopolysaccharide from Pseudomonas aeruginosa serotype O5. Eur J Biochem 2000; 267(6):1640–1650.PubMedGoogle Scholar
  29. 29.
    Hancock RE, Mutharia LM, Chan L et al. Pseudomonas aeruginosa isolates from patients with cystic fibrosis: A class of serum-sensitive, nontypeable strains deficient in lipopolysaccharide O side chains. Infect Immun 1983; 42(1):170–177.PubMedGoogle Scholar
  30. 30.
    Knirel YA. Polysaccharide antigens of Pseudomonas aeruginosa. CRC Crit Rev Microbiol 1990; 17:273–304.Google Scholar
  31. 31.
    Knirel YA, Vinogradov EV, Kocharova NA et al. The structure of O-specific polysaccharides and serological classification of Pseudomonas aeruginosa (a review). Acta Microbiol Hung 1988; 35(l):3–24.PubMedGoogle Scholar
  32. 32.
    Stanislavsky ES, Lam JS. Pseudomonas aeruginosa antigens as potential vaccines. FEMS Micro Rev 1997; 21(3):243–77.Google Scholar
  33. 33.
    Kuzio J, Kropinski AM. O-antigen conversion in Pseudomonas aeruginosa PAOl by bacteriophage D3. J Bacteriol 1983; 155(1):203–212.PubMedGoogle Scholar
  34. 34.
    Newton GJ, Daniels C, Burrows LL et al. Three-component-mediated serotype conversion in Pseudomonas aeruginosa by bacteriophage D3. Mol Microbiol 2001; 39(5):1237–1247.PubMedGoogle Scholar
  35. 35.
    Fisher MW, Devlin HB, Gnabski F. New immunotype schema for Pseudomonas aeruginosa based on protective antigens. J Bacteriol 1969; 98:835–836.PubMedGoogle Scholar
  36. 36.
    Matthews-Greer JM, Gilleland HE, Jr. Outer membrane protein F (porin) preparation of Pseudomonas aeruginosa as a protective vaccine against heterologous immunotype strains in a burned mouse model. J Infect Dis 1987; 155(6): 1282–1291.PubMedGoogle Scholar
  37. 37.
    Alexander JW, Fisher MW, MacMillan BG. Immunological control of Pseudomonas infection in burn patients: a clinical evaluation. Arch Surgery 1971; 102(l):31–35.Google Scholar
  38. 38.
    Young LS, Meyer RD, Armstrong D. Pseudomonas aeruginosa vaccine in cancer patients. Ann Intern Med 1973; 79(4):518–527.PubMedGoogle Scholar
  39. 39.
    Haghbin M, Armstrong D, Murphy ML. Controlled prospective trial of Pseudomonas aeruginosa vaccine in children with acute leukemia. Cancer 1973; 32(4):761–766.PubMedGoogle Scholar
  40. 40.
    Pennington JE, Reynolds HY, Wood RE et al. Use of a Pseudomonas aeruginosa vaccine in pateints with acute leukemia and cystic fibrosis. Am J Med 1975; 58(5):629–636.PubMedGoogle Scholar
  41. 41.
    Cryz SJ, Jr., Furer E, Germanier R. Protection against fatal Pseudomonas aeruginosa burn wound sepsis by immunization with lipopolysaccharide and high-molecular-weight polysaccharide. Infect Immun 1984; 43(3):795–799.PubMedGoogle Scholar
  42. 42.
    Cryz SJ, Jr., Furer E, Sadoff JC et al. Production and characterization of a human hyperimmune intravenous immunoglobulin against Pseudomonas aeruginosa and Klebsiella species. J Infect Dis 1991; 163(5):1055–1061.PubMedGoogle Scholar
  43. 43.
    Pier GB, Pollack M. Isolation, structure, and immunogenicity of Pseudomonas aeruginosa immunotype 4 high-molecular-weight polysaccharide. Infect Immun 1989; 57(2):426–431.PubMedGoogle Scholar
  44. 44.
    Pier GB, Thomas D, Small G et al. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide. Infect Immun 1989; 57(1):174–179.PubMedGoogle Scholar
  45. 45.
    Hatano K, Pier GB.Complex serology and immune response of mice to variant high-molecular-weight O polysaccharides isolated from Pseudomonas aeruginosa serogroup O2 strains. Infect Immun 1998; 66(8):3719–3726.PubMedGoogle Scholar
  46. 46.
    Hatano K, Boisot S, Desjardins D et al. Immunogenic and antigenic properties of a heptavalent high-molecular-weight O-polysaccharide vaccine derived from Pseudomonas aeruginosa. Infect Immun 1994; 62(9):3608–36l6.PubMedGoogle Scholar
  47. 47.
    Cryz SJ, Jr., Sadoff JC, Furer E. Octavalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Micro Pathogen 1989; 6(l):75-80.Google Scholar
  48. 48.
    Donta ST, Peduzzi P, Cross AS et al. Immunoprophylaxis against Klebsiella and Pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group. J Infect Dis 1996; 174(3):537–43.PubMedGoogle Scholar
  49. 49.
    Cryz SJ, Jr., Lang A, Rudeberg A et al. Immunization of cystic fibrosis patients with a Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Behring Inst Mitt 1997; (98):345–349.Google Scholar
  50. 50.
    Masoud H, Sadovskaya I, de Kievit T et al. Structural elucidation of the lipopolysaccharide core region of the O-chain-deficient mutant strain A28 from Pseudomonas aeruginosa serotype 06 (International Antigenic Typing Scheme). J Bacteriol 1995; 177(23):6718–6726.PubMedGoogle Scholar
  51. 51.
    Sadovskaya I, Brisson JR, Lam JS et al. Structural elucidation of the lipopolysaccharide core regions of the wild-type strain PAOl and O-chain-deflcient mutant strains AK1401 and AK1012 from Pseudomonas aeruginosa serotype O5. Eur J Biochem 1998; 255(3):673–684.PubMedGoogle Scholar
  52. 52.
    Knirel YA, Bystrova OV, Shashkov AS et al. Structural analysis of the lipopolysaccharide core of a rough, cystic fibrosis isolate of Pseudomonas aeruginosa. Eur J Biochem 2001; 268(17):4708–4719.PubMedGoogle Scholar
  53. 53.
    Terashima M, Uezumi I, Tomio T et al. A protective human monoclonal antibody directed to the outer core region of Pseudomonas aeruginosa lipopolysaccharide. Infect Immun 1991; 59(1): 1–6.PubMedGoogle Scholar
  54. 54.
    Rivera M, McGroarty EJ. Analysis of a common-antigen lipopolysaccharide from Pseudomonas aeruginosa. J Bacteriol 1989; 171:2244–2248.PubMedGoogle Scholar
  55. 55.
    Hatano K, Goldberg JB, Pier GB. Pseudomonas aeruginosa lipopolysaccharide: evidence that the O side chains and common antigens are on the same molecule. J Bacteriol 1993; 175(16):5117–5128.PubMedGoogle Scholar
  56. 56.
    Makarenko TA, Kocharova NA, Edvabnaya LS et al. Immunological studies of an artificial antigen with specificity of a common polysaccharide antigen of Pseudomonas aeruginosa. FEMS Immunol Med Micro 1993; 7(3):251–256.Google Scholar
  57. 57.
    Pollack M, Young LS. Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man. J Clin Invest 1979; 63:276–286.PubMedGoogle Scholar
  58. 58.
    Russell NJ, Gacesa P. Chemistry and biology of the alginate of mucoid strains of Pseudomonas aeruginosa in cystic fibrosis. Mol Aspects Med 1988; 10(1):1–91.PubMedGoogle Scholar
  59. 59.
    Sherbrock-Cox V, Russell NJ, Gacesa P. The purification and chemical characterisation of the alginate present in extracellular material produced by mucoid strains of Pseudomonas aeruginosa. Carbohydr Res 1984; 135(1): 147–154.PubMedGoogle Scholar
  60. 60.
    Pier GB, Small GJ, Warren HB. Protection against mucoid Pseudomonas aeruginosa in rodent models of endobronchial infections. Science 1990; 249(4968):537–540.PubMedGoogle Scholar
  61. 61.
    Johansen HK, Espersen F, Cryz SJ, Jr. et al. Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection. Infect Immun 1994; 62(8):3146–3155.PubMedGoogle Scholar
  62. 62.
    Pier GB, Saunders JM, Ames P et al. Opsonophagocytic killing antibody to Pseudomonas aeruginosa mucoid exopolysaccharide in older noncolonized patients with cystic fibrosis. New Engl J Med 1987; 317(13):793–798.PubMedGoogle Scholar
  63. 63.
    Garner CV, Desjardins D, Pier GB. Immunogenic properties of Pseudomonas aeruginosa mucoid exopolysaccharide. Infect Immun 1990; 58(6):1835–1842.PubMedGoogle Scholar
  64. 64.
    Pier GB, Takeda S, Grout M et al. Immune complexes from immunized mice and infected cystic fibrosis patients mediate murine and human T cell killing of hybridomas producing protective, opsonic antibody to Pseudomonas aeruginosa. J Clin Invest 1993; 91(3): 1079–1087.PubMedGoogle Scholar
  65. 65.
    Pier GB, Desjardin D, Grout M et al. Human immune response to Pseudomonas aeruginosa mucoid exopolysaccharide (alginate) vaccine. Infect Immun 1994; 62(9): 3972–3979.PubMedGoogle Scholar
  66. 66.
    Pier GB, Coleman F, Grout M et al. Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis. Infect Immun 2001; 69(3).1895–1901.PubMedGoogle Scholar
  67. 67.
    Sood RK, Salem NK, Fuller S et al. Sythesis and immunogenicity in mice of mucoexopolysaccharide -diphtheria toxoid (MEP-DTd) conjugate. In: Abstracts of the 34th Intersciences Conference on Antimicrobial Agents and Chemotherapy 1994; 23.Google Scholar
  68. 68.
    Brennan FR, Jones TD, Gilleland LB et al. Pseudomonas aeruginosa outer-membrane protein F epitopes are highly immunogenic in mice when expressed on a plant virus. Microbiology 1999; 145(Pt 1):211–220.PubMedGoogle Scholar
  69. 69.
    Mansouri E, Gabelsberger J, Knapp B et al. Safety and immunogenicity of a Pseudomonas aeruginosa hybrid outer membrane protein F-I vaccine in human volunteers. Infect Immun 1999; 67(3):1461–1470.PubMedGoogle Scholar
  70. 70.
    Matthews-Greer JM, Robertson DE, L.B. G et al. Pseudomonas aeruginosa outer membrane protein F produced in Escherichia coli retains vaccine efficacy. Curr Microbiol 1990; 20:171–175.Google Scholar
  71. 71.
    Gilleland HE, Jr., Parker MG, Matthews JM et al. Use of a purified outer membrane protein F (porin) preparation of Pseudomonas aeruginosa as a protective vaccine in mice. Infect Immun 1984; 44(l):49–54.PubMedGoogle Scholar
  72. 72.
    Fox CW, Campbell GD, Jr., Anderson WM et al. Preservation of pulmonary function by an outer membrane protein F vaccine. A study in rats with chronic pulmonary infection caused by Pseudomonas aeruginosa. Chest 1994; 105(5): 1545–1550.PubMedGoogle Scholar
  73. 73.
    von Specht BU, Knapp B, Muth G et al. Protection of immunocompromised mice against lethal infection with Pseudomonas aeruginosa by active or passive immunization with recombinant P. aeruginosa outer membrane protein F and outer membrane protein I fusion proteins. Infect Immun 1995; 63(5):1855–1862.PubMedGoogle Scholar
  74. 74.
    Knapp B, Hundt E, Lenz U et al. A recombinant hybrid outer membrane protein for vaccination against Pseudomonas aeruginosa. Vaccine 1999; 17(13–14): 1663–1666.PubMedGoogle Scholar
  75. 75.
    Hughes EE, Gilleland HE, Jr. Ability of synthetic peptides representing epitopes of outer membrane protein F of Pseudomonas aeruginosa to afford protection against P. aeruginosa infection in a murine acute pneumonia model. Vaccine 1995; 13(18):1750–1753.PubMedGoogle Scholar
  76. 76.
    Worgall S, Kikuchi T, Singh R et al. Protection against Pseudomonas aeruginosa chronic lung infection in mice by genetic immunization against outer membrane protein F (OprF) of P. aeruginosa. Infect Immun 2001; 69(7):4521–4527.PubMedGoogle Scholar
  77. 77.
    Toth A, Schodel F, Duchene M et al. Protection of immunosuppressed mice against translocation of Pseudomonas aeruginosa from the gut by oral immunization with recombinant Pseudomonas aeruginosa outer membrane protein I expressing Salmonella dulbin. Vaccine 1994; 12(13): 1215–1221.PubMedGoogle Scholar
  78. 78.
    Duchene M, Barron C, Schweizer A et al. Pseudomonas aeruginosa outer membrane lipoprotein I gene: molecular cloning, sequence, and expression in Escherichia coli. J Bacteriol 1989; 171(8):4130–4137.PubMedGoogle Scholar
  79. 79.
    Finke M, Duchene M, Eckhardt A et al. Protection against experimental Pseudomonas aeruginosa infection by recombinant P. aeruginosa lipoprotein I expressed in Escherichia coli. Infect Immun 1990; 58:2241–2244.PubMedGoogle Scholar
  80. 80.
    Mutharia LM, Nicas TI, Hancock RE. Outer membrane proteins of Pseudomonas aeruginosa serotype strains. J Infect Dis 1982; l46(6):770–779.Google Scholar
  81. 81.
    von Specht BU, Lucking HC, Blum B et al. Safety and immunogenicity of a Pseudomonas aeruginosa outer membrane protein I vaccine in human volunteers. Vaccine 1996; 14(12):1111–1117.Google Scholar
  82. 82.
    Jang IJ, Kim IS, Park WJ et al. Human immune response to a Pseudomonas aeruginosa outer membrane protein vaccine. Vaccine 1999; 17(2): 158–168.PubMedGoogle Scholar
  83. 83.
    Lee NG, Ahn BY, Jung SB et al. Human anti-Pseudomonas aeruginosa outer membrane proteins IgG cross-protective against infection with heterologous immunotype strains of P. aeruginosa. FEMS Immunol Med Micro 1999; 25(4):339–347.Google Scholar
  84. 84.
    Lee NG, Jung SB, Ahn BY et al. Protection of mice against P. aeruginosa infections by large-scale affinity-purified human IgG specific to P. aeruginosa outer membrane proteins. Vaccine 1999; 18(7–8):665–674.PubMedGoogle Scholar
  85. 85.
    Lee NG, Jung SB, Ahn BY et al. Immunization of burn-patients with a Pseudomonas aeruginosa outer membrane protein vaccine elicits antibodies with protective efficacy. Vaccine 2000; 18(18):1952–1961.PubMedGoogle Scholar
  86. 86.
    Kim DK, Kim JJ, Kim JH et al. Comparison of two immunization schedules for a Pseudomonas aeruginosa outer membrane proteins vaccine in burn patients. Vaccine 2001; 19(9–10): 1274–83.Google Scholar
  87. 87.
    Stanislavsky ES, Edvabnaya LS, Bandman OA et al. Experimental studies on the protective efficacy of a Pseudomonas aeruginosa vaccine. Vaccine 1989; 7:562–566.PubMedGoogle Scholar
  88. 88.
    Stanislavsky ES, Balayan SS, Sergienko AI et al. Clinicoimmunological trials of Pseudomonas aeruginosa vaccine. Vaccine 1991; 9(7):491–494.PubMedGoogle Scholar
  89. 89.
    Miler JM, Spilsbury JF, Jones RJ et al. A new polyvalent Pseudomonas vaccine. J Med Microbiol 1977; 10(l):19–27.PubMedGoogle Scholar
  90. 90.
    Pennington JE, Pier GB. Efficacy of cell wall Pseudomonas aeruginosa vaccines for protection against experimental pneumonia. Rev Infect Dis 1983; 5 Supp 5:S852–S857.PubMedGoogle Scholar
  91. 91.
    Jones RJ, Roe EA, Gupta JL. Controlled trial of Pseudomonas immunoglobulin and vaccine in burn patients. Lancet 1980; 2(8207): 1263–1265.PubMedGoogle Scholar
  92. 92.
    Maclntyre 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; 52(l):76–84.Google Scholar
  93. 93.
    Sato H, Okinaga K, Saito H. Role of pili in the pathogenesis of Pseudomonas aeruginosa burn infection. Microbiol Immunol 1988; 32(2): 131–139.PubMedGoogle Scholar
  94. 94.
    Montie TC, Anderson TR. Enzyme-linked immunosorbent assay for detection of Pseudomonas aeruginosa H (flagellar) antigen. Eur J Clin Microbiol Infect Dis 1988; 7:256–260.PubMedGoogle Scholar
  95. 95.
    Holder LA, Naglich JG. Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: Immunization using divalent flagella preparations. J Trauma 1986; 26:118–122.PubMedGoogle Scholar
  96. 96.
    Doering G, Dorner F. A multicenter vaccine trial using the Pseudomonas aeruginosa flagella vaccine IMMUNO in patients with cystic fibrosis. Behring Inst Mitt 1997; (98):338–44.Google Scholar
  97. 97.
    Doering G, Pfeiffer C, Weber U et al. Parenteral application of a Pseudomonas aeruginosa flagella vaccine elicits specific anti-flagella antibodies in the airways of healthy individuals. Am J Resp Crit Care Med 1995; 151 (4):983–5.Google Scholar
  98. 98.
    Ochi H, Ohtsuka H, Yokota S et al. Inhibitory activity on bacterial motility and in vivo protective activity of human monoclonal antibodies against flagella of Pseudomonas aeruginosa. Infect Immun 1991; 59(2):550–554.PubMedGoogle Scholar
  99. 99.
    Matsumoto T, Tateda K, Miyazaki S et al. Effect of antiflagellar human monoclonal antibody on gut-derived Pseudomonas aeruginosa sepsis in mice. Clin Diag Lab Immunol 1999; 6(4):537–54l.Google Scholar
  100. 100.
    Oishi K, Sonoda F, Iwagaki A et al. Therapeutic effects of a human antiflagella monoclonal antibody in a neutropenic murine model of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother 1993; 37(2):164–170.PubMedGoogle Scholar
  101. 101.
    Arora SK, Dasgupta N, Lory S et al. Identification of two distinct types of flagellar cap proteins, FliD, in Pseudomonas aeruginosa. Infect Immun 2000; 68(3):1474–1479.PubMedGoogle Scholar
  102. 102.
    Luzar MA, Montie TC. Avirulence and altered physiological properties of cystic fibrosis strains of Pseudomonas aeruginosa. Infect Immun 1985; 50(2):572–576.PubMedGoogle Scholar
  103. 103.
    Arora SK, Ritchings BW, Almira EC et al. The Pseudomonas aeruginosa flagellar cap protein, FliD, is responsible for mucin adhesion. Infect Immun 1998; 66(3):1000-1007.PubMedGoogle Scholar
  104. 104.
    Saiman L, Prince A. Pseudomonas aeruginosa pili bind to asialo-GMl which is increased on the surface of cystic fibrosis epithelial cells. J Clin Invest 1993; 92:1875–1880.PubMedGoogle Scholar
  105. 105.
    Comolli JC, Waite LL, Mostov KE et al. Pili binding to asialo-GMl on epithelial cells can mediate cytotoxicity or bacterial internalization by Pseudomonas aeruginosa. Infect Immun 1999; 67(7):3207–3214.PubMedGoogle Scholar
  106. 106.
    Cachia PJ, Glasier LM, Hodgins RR et al. The use of synthetic peptides in the design of a consensus sequence vaccine for Pseudomonas aeruginosa. J Peptide Res 1998; 52(4):289–299.Google Scholar
  107. 107.
    Hazes B, Sastry PA, Hayakawa K et al. Crystal structure of Pseudomonas aeruginosa PAK pilin suggests a main-chain-dominated mode of receptor binding. J Mol Biol 2000; 299(4): 1005–1017.PubMedGoogle Scholar
  108. 108.
    Cornells GR, Van Gijsegem F. Assembly and function of type III secretory systems. Annu Rev Microbiol 2000; 54:735–774.Google Scholar
  109. 109.
    Roy-Burman A, Savel RH, Racine S et al. Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections. J Infect Dis 2001; 83(12): 1767–1774.Google Scholar
  110. 110.
    Frank DW. The exoenzyme S regulon of Pseudomonas aeruginosa. Mol Micro 1997; 26(4):621–629.Google Scholar
  111. 111.
    Yahr TL, Vallis AJ, Hancock MK et al. ExoY, an adenylate cyclase secreted by the Pseudomonas aeruginoas type III system. Proc Nat Acad Sci 1998; 95(23):13899–13904.PubMedGoogle Scholar
  112. 112.
    Finck-Barbancon V, Goranson J, Zhu L et al. ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol Micro 1997; 25(3):547–557.Google Scholar
  113. 113.
    Hauser AR, Kang PJ, Engel JN. PepA, a secreted protein of Pseudomonas aeruginosa, is necessary for cytotoxicity and virulence. Mol Micro 1998; 27(4):807–818.Google Scholar
  114. 114.
    Holder IA, Neely AN, Frank DW. Type III secretion/intoxication system important in virulence of Pseudomonas aeruginosa infections in burns. Burns 2001; 27(2):129–130.PubMedGoogle Scholar
  115. 115.
    Kurahashi K, Kajikawa O, Sawa T et al. Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 1999; 104(6):743–750.PubMedGoogle Scholar
  116. 116.
    Allewelt M, Coleman FT, Grout M et al. Acquisition of expression of the P. aeruginosa ExoU cytotoxin leads to increased bacterial virulence in a murine model of acute pneumonia and systemic spread. Infect Immun 2000; 68:3998–4004.PubMedGoogle Scholar
  117. 117.
    Holmstrom A, Olsson J, Cherepanov P et al. LcrV is a channel size-determining component of the Yop effector translocon of Yersinia. Mol Micro 2001; 39(3):620–632.Google Scholar
  118. 118.
    Sawa T, Yahr TL, Ohara M et al. Active and passive immunization with the Pseudomonas V antigen protects against type III intoxication and lung injury. Nature Med 1999; 5(4):392–398.PubMedGoogle Scholar
  119. 119.
    Shime N, Sawa T, Fujimoto J et al. Therapeutic administration of anti-PcrV F(ab’)(2) in sepsis associated with Pseudomonas aeruginosa. J Immunol 2001; l67(10):5880–5886.Google Scholar
  120. 120.
    Holder IA, Neely AN, Frank DW. PcrV immunization enhances survival of burned Pseudomonas aeruginosa-infected mice. Infect Immun 2001; 69(9):5908–5910.PubMedGoogle Scholar
  121. 121.
    Pier GB, Grout M, Zaidi TS et al. Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Science 1996; 271(5245):64–67.PubMedGoogle Scholar
  122. 122.
    Sawa T, Ohara M, Kurahashi K et al. In vitro cellular toxicity predicts Pseudomonas aeruginosa virulence in lung infections. Infect Immun 1998; 66(7):3242–3249.PubMedGoogle Scholar
  123. 123.
    Pier GB, Grout M, Zaidi TS. Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung. Proc Nat Acad Sci 1997; 94(22):12088–12093.PubMedGoogle Scholar
  124. 124.
    Pier GB, Grout M, Zaidi TS et al. How mutant CFTR may contribute to Pseudomonas aeruginosa infection in cystic fibrosis. Am J Resp Crit Care Med 1996; 154(4 Pt 2):S175–S182.PubMedGoogle Scholar
  125. 125.
    Zaidi TS, Lyczak J, Preston M et al. Cystic fibrosis transmembrane conductance regulator-mediated corneal epithelial cell ingestion of Pseudomonas aeruginosa is a key component in the pathogenesis of experimental murine keratitis. Infect Immun 1999; 67(3):1481–1492.PubMedGoogle Scholar
  126. 126.
    Kupiec-Weglinski JW, Austyn JM, Morris PJ. Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues. J Exp Med 1988; l67(2):632–645.Google Scholar
  127. 127.
    Banchereau J, Briere F, Caux C et al. Immunobiology of dendritic cells. Ann Rev Immunol 2000; 18:767–811.Google Scholar
  128. 128.
    Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998; 392(6671):86–89.PubMedGoogle Scholar
  129. 129.
    Dhodapkar MV, Steinman RM, Sapp M et al. Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J Clin Invest 1999; 104(2): 173–180.PubMedGoogle Scholar
  130. 130.
    Cannon CL, Stopak K, Pier GB. Defective apoptosis of lung cells expressing mutant CFTR after infection with Pseudomonas aeruginosa. In: North American Cystic Fibrosis Meeting; 1999.Google Scholar
  131. 131.
    Hauser AR, Engel JN. Pseudomonas aeruginosa induces type-III-secretion-mediated apoptosis of macrophages and epithelial cells. Infect Immun 1999; 67(10):5530–5537.PubMedGoogle Scholar
  132. 132.
    Grassme H, Kirschnek S, Riethmueller J et al. CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 2000; 290(5491):527–530.PubMedGoogle Scholar
  133. 133.
    Stenger S, Hanson DA, Teitelbaum R et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 1998; 282(5386): 121–125.PubMedGoogle Scholar
  134. 134.
    Silva CL, Lowrie DB. Identification and characterization of murine cytotoxic T cells that kill Mycobacterium tuberculosis. Infect Immun 2000; 68(6):3269–3274.PubMedGoogle Scholar
  135. 135.
    Lo WF, Ong H, Metealf ES et al. T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to M. tuberculosis infection and the involvement of MHC class lb molecules. J Immunol 1999; 162(9):5398–5406.PubMedGoogle Scholar
  136. 136.
    Leef M, Elkins KL, Barbie J et al. Protective immunity to Bordetella pertussis requires both B cells and CD4(+) T cells for key functions other than specific antibody production. J Exp Med 2000; 191(11):1841–1852.PubMedGoogle Scholar
  137. 137.
    Wang J, Fan X, Lindholm C et al. Helicobacter pylori modulates lymphoepithelial cell interactions leading to epithelial cell damage through Fas/Fas ligand interactions. Infect Immun 2000; 68(7):4303–4311.PubMedGoogle Scholar
  138. 138.
    Markham RB, Pier GB. Characterization of the antibody response in inbred mice to a high-molecular-weight polysaccharide from Pseudomonas aeruginosa immunotype 1. Infect Immun 1983; 41(l):232–236.PubMedGoogle Scholar
  139. 139.
    Markham RB, Goellner J, Pier GB. In vitro T cell-mediated killing of Pseudomonas aeruginosa. I. Evidence that a lymphokine mediates killing. J Immunol 1984; 133(2):962–968.PubMedGoogle Scholar
  140. 140.
    Markham RB, Pier GB, Goellner JJ et al. In vitro T cell-mediated killing of Pseudomonas aeruginosa. II. The role of macrophages and T cell subsets in T cell killing. J Immunol 1985; 134(6):4112–4117.PubMedGoogle Scholar
  141. 141.
    Markham RB, Pier GB, Powderly WG. Suppressor T cells regulating the cell-mediated immune response to Pseudomonas aeruginosa can be generated by immunization with anti-bacterial T cells. J Immunol 1988; 141(11):3975–3979.PubMedGoogle Scholar
  142. 142.
    Markham RB, Powderly WG. Exposure of mice to live Pseudomonas aeruginosa generates protective cell-mediated immunity in the absence of an antibody response. J Immunol 1988; 140:2039–2045.PubMedGoogle Scholar
  143. 143.
    Markham RB, Pier GB, Schreiber JR. The role of cytophilic IgG3 antibody in T cell-mediated resistance to infection with the extracellular bacterium, Pseudomonas aeruginosa. J Immunol 1991; l46(l):316–320.Google Scholar
  144. 144.
    Markham RB, Pier GB. Immunologic basis for mouse protection provided by high-molecular-weight polysaccharide from immunotype 1 Pseudomonas aeruginosa. Rev Infect Dis 1983; 5 Supp 5:S957–S962.PubMedGoogle Scholar
  145. 145.
    Pier GB, Markham RB. Induction in mice of cell-mediated immunity to Pseudomonas aeruginosa by high molecular weight polysaccharide and vinblastine. J Immunol 1982; 128(5):2121–2125.PubMedGoogle Scholar
  146. 146.
    Pier GB, Markham RB, Eardley D. Correlation of the biologic responses of C3H/HEJ mice to endotoxin with the chemical and structural properties of the lipopolysaccharides from Pseudomonas aeruginosa and Escherichia coli. J Immunol 1981; 127(1): 184–191.PubMedGoogle Scholar
  147. 147.
    Powderly WG, Pier GB, Markham RB. In vitro T cell-mediated killing of Pseudomonas aeruginosa. IV. Noneresposiveness in polysaccharide-immunized BALB/c mice is attributable to vinblastine-sensitive suppressor T cells. J Immunol 1986; 137(6):2025–2030.PubMedGoogle Scholar
  148. 148.
    Powderly WG, Pier GB, Markham RB. T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice. J Clin Invest 1986; 78(2):375–380.PubMedGoogle Scholar
  149. 149.
    Powderly WG, Pier GB, Markham RB. In vitro T cell-mediated killing of Pseudomonas aeruginosa. III. The role of suppressor T cells in nonresponder mice. J Immunol 1986; 136(l):299–303.PubMedGoogle Scholar
  150. 150.
    Powderly WG, Pier GB, Markham RB. In vitro T cell-mediated killing of Pseudomonas aeruginosa. V. Generation of bactericidal T cells in nonresponder mice. J Immunol 1987; 138(7):2272–2277.PubMedGoogle Scholar
  151. 151.
    Powderly WG, Schreiber JR, Pier GB et al. T cells recognizing polysaccharide-specific B cells function as contrasuppressor cells in the generation of T cell immunity to Pseudomonas aeruginosa. J Immunol 1988; l40(8):2746–2752.Google Scholar
  152. 152.
    Dunkley ML, Clancy RL, Cripps AW. A role for CD4+ T cells from orally immunized rats in enhanced clearance of Pseudomonas aeruginosa from the lung. Immunology 1994; 83(3):362–369.PubMedGoogle Scholar
  153. 153.
    Dunkley ML, Cripps AW, Clancy RL. Immunity to respiratory Pseudomonas aeruginosa infection: P. aeruginosa-specific T cells arising after intestinal immunization. Adv Exp Med Biol 1995; 371B:755–759.PubMedGoogle Scholar
  154. 154.
    Parmely MJ, Iglewski BH, Horvat RT. Identification of the principal T lymphocyte-stimulating antigens of Pseudomonas aeruginosa. J Exp Med 1984; 160(5): 1338–1349.PubMedGoogle Scholar
  155. 155.
    Mody CH, Buser DE, Syme RM et al. Pseudomonas aeruginosa exoenzyme S induces proliferation of human T lymphocytes. Infect Immun 1995; 63(5):1800–1805.PubMedGoogle Scholar
  156. 156.
    Bruno TF, Woods DE, Mody CH. Exoenzyme S from Pseudomonas aeruginosa induces apoptosis in T lymphocytes. J Leukocyte Biol 2000; 67(6):808–816.PubMedGoogle Scholar
  157. 157.
    Ulmer AJ, Pryjma J, Tarnok Z et al. Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes. Infect Immun 1990; 58(3):808–815.PubMedGoogle Scholar
  158. 158.
    Kondratieva TK, Kobets NV, Khaidukov SV et al. Characterization of T cell clones derived from lymph nodes and lungs of Pseudomonas aeruginosa-susceptible and resistant mice following immunization with heat-killed bacteria. Clin Exp Immunol 2000; 121(2):275–282.PubMedGoogle Scholar
  159. 159.
    Stevenson MM, Kondratieva TK, Apt AS et al. In vitro and in vivo T cell responses in mice during bronchopulmonary infection with mucoid Pseudomonas aeruginosa. Clin Exp Immunol 1995; 99:98–105.PubMedGoogle Scholar
  160. 160.
    Tarn M, Snipes GJ, Stevenson MM. Characterization of chronic bronchopulmonary Pseudomonas aeruginosa infection in resistant and susceptible inbred mouse strains. Am J Resp Cell Mol Biol 1999; 20(4):710–719.Google Scholar
  161. 161.
    Moser C, Johansen HK, Song Z et al. Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Thl responding C3H/HeN mice. APMIS 1997; 105(11):838–842.PubMedGoogle Scholar
  162. 162.
    Sawa T, Corry DB, Gropper MA et al. IL-10 improves lung injury and survival in Pseudomonas aeruginosa pneumonia. J Immunol 1997; 159(6):2858–2866.PubMedGoogle Scholar
  163. 163.
    Hazlett LD, McClellan S, Kwon B et al. Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Thl versus Th2 responsive. Invest Ophth Vis Sci 2000; 41(3):805–810.Google Scholar
  164. 164.
    Kwon B, Hazlett LD. Association of CD4+ T cell-dependent keratitis with genetic susceptibility to Pseudomonas aeruginosa ocular infection. J Immunol 1997; 159(12):6283–6290.PubMedGoogle Scholar
  165. 165.
    Griffith TS, Brunner T, Fletcher SM et al. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 1995; 270(5239):1189–1192.PubMedGoogle Scholar
  166. 166.
    Stuart PM, Griffith TS, Usui N et al. CD95 ligand (FasL)-induced apoptosis is necessary for corneal allograft survival. J Clin Invest 1997; 99(3):396–402.PubMedGoogle Scholar
  167. 167.
    Gao Y, Herndon JM, Zhang H et al. Anti-inflammatory effects of CD95 ligand (FasL)-induced apoptosis. J Exp Med 1998; 188(5):887-896.PubMedGoogle Scholar
  168. 168.
    Durieu I, Amsellem C, Paulin C et al. Fas and Fas ligand expression in cystic fibrosis airway epithelium. Thorax 1999; 54(12):1093–1098.PubMedGoogle Scholar
  169. 169.
    Sorensen RU, Stern RC, Polmar SH. Cellular immunity to bacteria: Impairment of in vitro lymphocyte responses to Pseudomonas aeruginosa in cystic fibrosis patients. Infect Immun 1977; 18(3):735–740.PubMedGoogle Scholar
  170. 170.
    Sorensen RU, Stern RC, Polmar SH. Lymphocyte responsiveness to Pseudomonas aeruginosa in cystic fibrosis: Relationship to status of pulmonary disease in sibling pairs. J Pediatr 1978; 93(2):201–205.PubMedGoogle Scholar
  171. 171.
    Knutsen AP, Slavin RG, Roodman ST et al. Decreased T helper cell function in patients with cystic fibrosis. Int Arch Allergy Appl Immunol 1988; 85(2):208-212.PubMedGoogle Scholar
  172. 172.
    Chen JH, Schulman H, Gardner P. A cAMP-regulated chloride channel in lymphocytes that is affected in cystic fibrosis. Science 1989; 243(4891):657-660.PubMedGoogle Scholar
  173. 173.
    Dong YJ, Chao AC, Kouyama K et al. Activation of CFTR chloride current by nitric oxide in human T lymphocytes. EMBO J 1995; l4(12):2700–2707.Google Scholar
  174. 174.
    Krauss RD, Bubien JK, Drumm ML et al. Transfection of wild-type CFTR into cystic fibrosis lymphocytes restores chloride conductance at G1 of the cell cycle. Embo J 1992; 11(3):875–883.PubMedGoogle Scholar
  175. 175.
    Moss RB, Bocian RC, Hsu YP et al. Reduced IL-10 secretion by CD4+ T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR). Clin Exp Immunol 1996; 106(2):374–388.PubMedGoogle Scholar
  176. 176.
    Moss RB, Hsu YP, Olds L. Cytokine dysregulation in activated cystic fibrosis (CF) peripheral lymphocytes. Clin Exp Immunol 2000; 120(3):518–525.PubMedGoogle Scholar
  177. 177.
    Worgall S, Kikuchi T, Singh R et al. Protection against pulmonary infection with Pseudomonas aeruginosa following immunization with P. aeruginosa-pulsed dendritic cells. Infect Immun 2001; 69(7):4521–4527.PubMedGoogle Scholar
  178. 178.
    Kikuchi T, Worgall S, Singh R et al. Dendritic cells genetically modified to express CD40 ligand and pulsed with antigen can initiate antigen-specific humoral immunity independent of CD4+ T cells. Nature Med 2000; 6(10):1154–1159.PubMedGoogle Scholar
  179. 179.
    Kikuchi T, Hackett NR, Crystal RG. Cross-strain protection against clinical and laboratory strains of Pseudomonas aeruginosa mediated by dendritic cells genetically modified to express CD40 ligand and pulsed with specific strains of Pseudomonas aeruginosa. Hum Gene Ther 2001; 12(10):1251–1263.PubMedGoogle Scholar
  180. 180.
    Kikuchi T, Crystal RG. Antigen-pulsed dendritic cells expressing macrophage-derived chemokine elicit Th2 responses and promote specific humoral immunity. J Clin Invest 2001; 108(6):917–927.PubMedGoogle Scholar
  181. 181.
    Dubois B, Vanbervliet B, Fayette J et al. Dendritic cells enhance growth and differentiation of CD40-activated B lymphocytes. J Exp Med 1997; 185(5):941–951.PubMedGoogle Scholar
  182. 182.
    Dubois B, Massacrier C, Vanbervliet B et al. Critical role of IL-12 in dendritic cell-induced differentiation of naive B lymphocytes. J Immunol 1998; 161(5):2223–2231.PubMedGoogle Scholar
  183. 183.
    Van Kooten C, Banchereau J. CD40-CD40 ligand: a multifunctional receptor-ligand pair. Adv Immunol 1996; 61:1-77.PubMedGoogle Scholar
  184. 184.
    Brown MP, Topham DJ, Sangster MY et al. Thymic lymphoproliferative disease after successful correction of CD40 ligand deficiency by gene transfer in mice. Nature Med 1998; 4(11): 1253–1260.PubMedGoogle Scholar
  185. 185.
    Wiley JA, Geha R, Harmsen AG. Exogenous CD40 ligand induces a pulmonary inflammation response. J Immunol 1997; 158(6):2932–2938.PubMedGoogle Scholar
  186. 186.
    Gonzalo JA, Pan Y, Lloyd CM et al. Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation. J Immunol 1999; 163(1):403–411.PubMedGoogle Scholar
  187. 187.
    Stocker BA. Auxotrophic M. tuberculosis typhi as live vaccine. Vaccine 1988; 6(2): 141–145.PubMedGoogle Scholar
  188. 188.
    Hernanz Moral C, Flano del Castillo E, Lopez Fierro P et al. Molecular characterization of the Aeromonas hydrophila aroA gene and potential use of an auxotrophic aroA mutant as a live attenuated vaccine. Infect Immun 1998; 66(5): 1813-1821.PubMedGoogle Scholar
  189. 189.
    Poirier TP, Kehoe MA, Beachey EH. Protective immunity evoked by oral administration of attenuated aroA Salmonella typhimurium expressing cloned streptococcal M protein. J Exp Med 1988; 168:25–32.PubMedGoogle Scholar
  190. 190.
    Lo-Man R, Langeveld JPM, Deriaud E et al. Extending the CD4+ T-Cell epitope specificity of the Thl immune response to an antigen using a Salmonella enterica serovar Typhimurium delivery vehicle. Infect Immun 2000; 68(6):3079–3089.PubMedGoogle Scholar
  191. 191.
    Priebe GP, Brinig MM, Hatano K et al. Construction and characterization of a live, attenuated aroA deletion mutant of Pseudomonas aeruginosa as a candidate intranasal vaccine. Infect Immun 2002; 70(3):1507–1517.PubMedGoogle Scholar
  192. 192.
    Jones RJ, Roe EA, Gupta JL. Controlled trials of a polyvalent Pseudomonas vaccine in burns. Lancet 1979; 2(8150):977–82.PubMedGoogle Scholar
  193. 193.
    Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient Registry 2000 Annual Report. Bethesda, MD; September, 2001.Google Scholar
  194. 194.
    Ramsey BW, Pepe MS, Quan JM et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med 1999; 340(l):23–30.PubMedGoogle Scholar

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© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Gregory P. Priebe
  • Gerald B. Pier

There are no affiliations available

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