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Infect. Immun. doi:10.1128/IAI.00496-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Prophylactic and therapeutic efficacy in murine keratitis infection of a fully human IgG1 monoclonal antibody to Pseudomonas aeruginosa alginate

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

^* To whom correspondence should be addressed. Email: gpier{at}channing.harvard.edu.

	Abstract

Treatment of ulcerative keratitis due to Pseudomonas aeruginosa is difficult, time consuming and uncomfortable owing to the need for frequent application of antibiotic drops to the infected corneal surface. Here we examined whether a fully human IgG1 monoclonal antibody (mAb) specific to the conserved alginate surface polysaccharide of P. aeruginosa could mediate protective immunity against typically non-mucoid strains isolated from human cases of keratitis. mAb F429 effectively opsonized alginate-positive, but not alginate-negative, non-mucoid strains in conjunction with phagocytes and complement. Prophylactic administration of mAb F429 18 hr prior to infection with 2 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 hr post-infection in both experimental protocols resulted in significant reductions in bacteria in the eye as well as minimizing pathologic 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.