Prophylactic and therapeutic efficacy of a fully human immunoglobulin G1 monoclonal antibody to Pseudomonas aeruginosa alginate in murine keratitis infection.
Treatment of ulcerative keratitis due to Pseudomonas aeruginosa is difficult, time-consuming, and uncomfortable owing to the need for the frequent application of antibiotic drops to the infected corneal surface. We examined here whether a fully human immunoglobulin G1 monoclonal antibody (MAb) specific to the conserved alginate surface polysaccharide of P. aeruginosa could mediate protective immunity against typically nonmucoid strains isolated from human cases of keratitis. MAb F429 effectively opsonized alginate-positive, but not alginate-negative, nonmucoid strains in conjunction with phagocytes and complement. Prophylactic administration of MAb F429 18 h prior to infection with two clinical isolates significantly reduced bacterial levels in the eye and the associated corneal pathology. Along similar lines, systemic intraperitoneal injection, as well as topical application of the MAb onto the infected eye, starting 8 h postinfection in both experimental protocols resulted in significant reductions in bacteria in the eye, as well as minimizing pathological damage to the cornea. These findings indicate that MAb F429 could be useful as an additional therapeutic component for the treatment of P. aeruginosa keratitis.
Zaidi
Tanweer
T
Department of Medicine, Channing Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Pier
Gerald B
GB
D000464:Alginates; D000818:Animals; D000907:Antibodies, Bacterial / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003165:Complement System Proteins / Q000276:immunology; D003315:Cornea / Q000382:microbiology / Q000473:pathology; D020723:Glucuronic Acid / Q000037:antagonists & inhibitors; D006603:Hexuronic Acids / Q000037:antagonists & inhibitors; D006801:Humans; D007634:Keratitis / Q000188:drug therapy* / Q000517:prevention & control*; D051379:Mice; D050296:Microbial Viability; D009895:Opsonin Proteins / Q000627:therapeutic use; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D000464:Alginates; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D006603:Hexuronic Acids; D009895:Opsonin Proteins; D020723:Glucuronic Acid; D003165:Complement System Proteins