Therapeutic administration of anti-PcrV F(ab ')(2) in sepsis associated with Pseudomonas aeruginosa

The effects of rabbit-derived polyclonal Ab against PcrV, a protein involve d in the translocation of type III secreted toxins of Pseudomonas aeruginos a, was investigated in two animal models of P. aeruginosa sepsis. In a mous e survival study, the i.v. administration of anti-PcrV IgG after the airspa ce instillation of a lethal dose of A aeruginosa resulted ill the complete survival of the animals. In a rabbit model of septic shock associated with Pseudomonas-induced lung injury, animals treated with anti-PcrV IgG intratr acheally or Lv. had significant decreases in lung injury, bacteremia, and p lasma TNF-alpha and significant improvement in the hemodynamic parameters a ssociated with shock compared with animals treated in a similar manner with nonspecific control IgG. The administration of anti-PcrV F(ab')(2) showed protective effects comparable to those of whole anti-PcrV IgG. These result s document that the therapeutic administration of anti-PcrV IgG blocks the type III secretion system-mediated virulence of P. aeruginosa and prevents septic shock and death, and that these protective effects are largely Fc in dependent. We conclude that. Ab therapy neutralizing the type III secretion system has significant potential against lethal P. aeruginosa infections.