Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection
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Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection. / Johansen, H K; Espersen, F; Cryz, S J; Hougen, H P; Fomsgaard, Anette; Rygaard, J; Høiby, N.
In: Infection and Immunity, Vol. 62, No. 8, 1994, p. 3146-55.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection
AU - Johansen, H K
AU - Espersen, F
AU - Cryz, S J
AU - Hougen, H P
AU - Fomsgaard, Anette
AU - Rygaard, J
AU - Høiby, N
PY - 1994
Y1 - 1994
N2 - Pseudomonas aeruginosa is the predominant pathogen in patients with cystic fibrosis (CF). To study the possibility of preventing lung inflammation and decreasing the progression of the infection by vaccination, we have developed a rat model of chronic P. aeruginosa lung infection. Rats were immunized with P. aeruginosa whole-cell sonicates, O-polysaccharide toxin A conjugate, an alginate-toxin A conjugate, or native alginate. Control animals received sterile saline or incomplete Freund's adjuvant (IFA). The macroscopic (mean score, 2.4 versus 2.7 to 3.2) (P <0.05) and microscopic (mean score, 2.0 versus 2.1 to 2.8) pathologic abnormalities were less severe in the control rats injected with sterile saline than in the immunized rats and the IFA group. The more severe lung abnormalities observed in immunized rats could be due to the result of immune complex-mediated lung tissue damage. The histopathologic results in the saline control rats were characterized by acute inflammation dominated by numerous polymorphonuclear leukocytes surrounding the alginate beads (microcolonies), as in CF patients. In contrast, the inflammatory response in the IFA group and in the immunized rats had changed from an acute-type inflammation to a chronic-type inflammation dominated by mononuclear leukocytes and scattered granulomas. Cross-reacting antibodies were induced by the two alginate vaccines, and most immunized animals developed a significant (P <0.001) antibody titer elevation (in enzyme-linked immunosorbent assay) of the immunoglobulin M (IgM), IgG, and IgA classes against the homologous antigens. The bacterial clearance was significantly (P <0.05) more efficient in most immunized rats than in the control rats given sterile saline. The present study shows that none of the vaccines could completely prevent chronic lung inflammation 4 weeks after challenge. However, the changed pathologic condition in immunized rats to a chronic-type inflammation might be of great benefit in future management of CF patients since the developing lung tissue damage has been shown to be caused by polymorphonuclear leukocyte-released elastase.
AB - Pseudomonas aeruginosa is the predominant pathogen in patients with cystic fibrosis (CF). To study the possibility of preventing lung inflammation and decreasing the progression of the infection by vaccination, we have developed a rat model of chronic P. aeruginosa lung infection. Rats were immunized with P. aeruginosa whole-cell sonicates, O-polysaccharide toxin A conjugate, an alginate-toxin A conjugate, or native alginate. Control animals received sterile saline or incomplete Freund's adjuvant (IFA). The macroscopic (mean score, 2.4 versus 2.7 to 3.2) (P <0.05) and microscopic (mean score, 2.0 versus 2.1 to 2.8) pathologic abnormalities were less severe in the control rats injected with sterile saline than in the immunized rats and the IFA group. The more severe lung abnormalities observed in immunized rats could be due to the result of immune complex-mediated lung tissue damage. The histopathologic results in the saline control rats were characterized by acute inflammation dominated by numerous polymorphonuclear leukocytes surrounding the alginate beads (microcolonies), as in CF patients. In contrast, the inflammatory response in the IFA group and in the immunized rats had changed from an acute-type inflammation to a chronic-type inflammation dominated by mononuclear leukocytes and scattered granulomas. Cross-reacting antibodies were induced by the two alginate vaccines, and most immunized animals developed a significant (P <0.001) antibody titer elevation (in enzyme-linked immunosorbent assay) of the immunoglobulin M (IgM), IgG, and IgA classes against the homologous antigens. The bacterial clearance was significantly (P <0.05) more efficient in most immunized rats than in the control rats given sterile saline. The present study shows that none of the vaccines could completely prevent chronic lung inflammation 4 weeks after challenge. However, the changed pathologic condition in immunized rats to a chronic-type inflammation might be of great benefit in future management of CF patients since the developing lung tissue damage has been shown to be caused by polymorphonuclear leukocyte-released elastase.
KW - Animals
KW - Antibodies, Bacterial
KW - Bacterial Vaccines
KW - Female
KW - Freund's Adjuvant
KW - Immunization
KW - Lung
KW - Pseudomonas Infections
KW - Pseudomonas aeruginosa
KW - Rats
KW - Rats, Sprague-Dawley
M3 - Journal article
C2 - 8039883
VL - 62
SP - 3146
EP - 3155
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 8
ER -
ID: 44354927