Feasibility of prophylaxis and therapy against gram-negative infections by human monoclonal antibodies.
In a murine model of Gram-negative sepsis, we have shown that the prophylactic application of human monoclonal antibodies (HmAbs) with specificity for lipopolysaccharides (LPS) of Pseudomonas aeruginosa protected against bacterial infection. In this paper we show that the therapeutical application of 5 micrograms of these HmAbs up to 6 h after challenge with a lethal dose of live P. aeruginosa results in a protection rate of 70-90%. Administration 18 h after bacterial challenge, diminished the protection to 43% survival rate. Furthermore, using a mixture of HmAbs recognizing a total of six different P. aeruginosa serotypes, no interference in their protective capacities was found. Finally, these HmAbs also protected galactosamine-sensitized mice against lethal challenge with LPS. Our data show that the described HmAbs confer bactericidal activity as well as anti-endotoxic activity in vivo.
Lang
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AB
Department of Immunology, Swiss Serum and Vaccine Institute, Bern, Switzerland.
Fürer
E
E
Cryz
S J
SJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007167:Immunotherapy; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000517:prevention & control / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides