Treatment of experimental Pseudomonas aeruginosa pneumonia with a human IgM monoclonal antibody.
A human IgM monoclonal antibody (MA-1C1) to Fisher immunotype 3 Pseudomonas aeruginosa lipopolysaccharide antigen was evaluated for in vivo activity in a guinea pig model of experimental pneumonia. Pharmacokinetics of MA-1C1 were compared in infected and noninfected animals. Intravenous bolus infusion of MA-1C1, 1 mg/kg, resulted in peak serum antibody concentrations of 3.8 +/- 0.08 and 3.7 +/- 0.05 micrograms/ml in infected and noninfected animals, respectively. Serum half-lives were 25 and 22 h in infected and noninfected groups. Treatment with a single intravenous infusion of MA-1C1 improved survival from pneumonia and was effective over a broad dose range (0.1-2.5 mg/kg). Cumulative survivals were 18 of 47 in the MA-1C1 group and 0 of 31 in controls (P less than .001). Treatment with MA-1C1 also resulted in fewer positive blood cultures 12 h after infection (P = .04). Although MA-1C1 penetrated into inflamed bronchial fluids, local concentrations were only 5% of the concentrations achieved in serum. Thus, MA-1C1 seems to provide significant therapeutic activity against experimental P. aeruginosa pneumonia by preventing dissemination of infection from the lung.
Pre-Clinical Microbiology and Immunology Department, Cutter Biological, Miles Inc., Berkeley, California.
R F
RF
Hector
M S
MS
Collins
J E
JE
Pennington
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage; D007167:Immunotherapy; D008070:Lipopolysaccharides / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology* / Q000628:therapy; D011552:Pseudomonas Infections / Q000276:immunology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D008070:Lipopolysaccharides