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2018 Agenda and Abstracts | < Previous Next >

2018 OMIG Abstract

A Multifunctional Bispecific Antibody Effective Against Pseudomonas Keratitis

Wesley Hebert1, Michael E. Zegans1, Antonio DiGiandomenico2
1Department of Surgery (Ophthalmology) and Microbiology and Immunology, Geisel School of Medicine at Dartmouth School, Hanover, NH, 2MedImmune, LLC, One MedImmune Way, Gaithersburg, MD


Purpose: A worrisome trend in the study and treatment of infectious disease noted in recent years is the increase in multidrug resistant strains of bacteria concurrent with a scarcity of new antimicrobial agents to counteract this rise. This is particularly true amongst bacteria within the ESKAPE designation (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Pseudomonas aeruginosa is one of the most common causes of bacterial keratitis. Therefore, it is vital to characterize and develop new antimicrobial agents with anti-Pseudomonas activity for use with the ocular surface.

Methods: MEDI3902 is a bispecific antibody targeting the P. aeruginosa Psl exopolysaccharide and the PcrV component of the type-3-secretion system. We initially assessed MEDI3902 for ocular surface toxicity. The antimicrobial activity of MEDI3902 was then tested on mice that had Pseudomonas keratitis from lab strain PAO1 which had been established by means of a corneal scratch model. MEDI3902 was evaluated for its ability to prevent infection topically after a bacterial challenge with a concurrent corneal scratch. We also tested the ability of MEDI3902 to treat established corneal infections when delivered via intravenous tail injections. Mice were scored clinically for the appearance of the epithelium and the opacification surrounding the corneal ulcer. For the prevention study, colony forming units (CFUs) were measured after treatment.

Results: MEDI3902 was non-toxic to the ocular surface and was effective compared to control antibody in preventing Pseudomonas keratitis with a onetime topical treatment at the time of infection. Both topical and intravenous administration of MEDI3902 was effective in treating established keratitis infections, significantly accelerating the bacterial resolution compared to the IgG control.

Conclusion: We report the use of a multifunctional bispecific monoclonal antibody targeted towards Psl and PcrV as an antimicrobial agent on the ocular surface.

Disclosure: S: Supported by a grant to Michael Zegans from MedImmune; E: Antonio DiGiandomenico is a research scientist at MedImmune


2018 Agenda and Abstracts | < Previous Next >