VACCINATION PROMOTES TH1-LIKE INFLAMMATION AND SURVIVAL IN CHRONIC PSEUDOMONAS-AERUGINOSA PNEUMONIA IN RATS

In a rat model of chronic Pseudomonas aeruginosa lung infection mimick ing cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a dep olymerized alginate toxin A conjugate (D-ALG toxin A), purified algina te, an O-polysaccharide toxin A conjugate, or sterile saline. After ch allenge none of the rats immunized with D-ALG toxin A died, in contras t to the other two vaccine groups combined (p = 0.03). A significant r eduction in the severity of the macroscopic lung inflammation was seen in rats immunized with D-ALG toxin A, compared with the other three g roups (p = 0.009). The histopathologic response in the control rats wa s dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after chal lenge from predominantly PMNs (TH2-like) to a chronic-type inflammatio n dominated by mononuclear leukocytes (TH1-like). In accordance, the a ntibody titers induced by the D-ALG toxin A vaccine were not different from those of the control rats after challenge. This study identifies a possible new way of modifying the inflammation and thereby preventi ng the PMN-mediated lung tissue damage during chronic P. aeruginosa lu ng infection in CF.