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Multifunctional Monoclonal Antibody Targeting Keratitis in Mice

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Date 2020 Nov 5
PMID 33147726
Citations 4
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Abstract

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 , , , , , and Enterobacter species (ESKAPE) designation. is one of the most common causes of bacterial keratitis. Therefore, it is of vital importance to characterize new antimicrobial agents with anti-Pseudomonal activity for use with the ocular surface. MEDI3902 is a multifunctional antibody that targets the persistence factor Psl exopolysaccharide, and the type 3 secretion protein PcrV. We initially assessed this antibody for ocular surface toxicity. The antimicrobial activity of the antibody was then tested by treating mice with established keratitis with both topical and intravenous treatment modalities. MEDI3902, was shown to be non-toxic to the ocular surface of mice when given topically. It was also effective compared to the control antibody at preventing keratitis with a one-time treatment at the time of infection. Both topical and intravenous administration of MEDI3902 has been proved significant in treating established keratitis infections as well, speeding the resolution of infection significantly more than that of the control IgG. We report the first use of a topical immunotherapeutic multifunctional agent targeting Psl and type 3 secretion on the ocular surface as an antimicrobial agent. While MEDI3902 has been shown to prevent biofilm formation in keratitis models when given prophylactically intravitally, we show that MEDI3902 has the capability to also treat an active infection when given intravenously to mice with keratitis. Our data indicate antibodies are well tolerated and nontoxic on the ocular surface. They reduce infection in mice treated concurrently at inoculation and reduced the signs of cornea pathology in mice with established infection. Taken together, these data indicate treatment with monoclonal antibodies directed against Psl and PcrV may be clinically effective in the treatment of keratitis and suggest that the design of further antibodies to be an additional tool in the treatment of bacterial keratitis.

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References
1.
Sorrentino M, Powers T . Effectiveness of palivizumab: evaluation of outcomes from the 1998 to 1999 respiratory syncytial virus season. The Palivizumab Outcomes Study Group. Pediatr Infect Dis J. 2000; 19(11):1068-71. DOI: 10.1097/00006454-200011000-00007. View

2.
McMorran B, Town L, Costelloe E, Palmer J, Engel J, Hume D . Effector ExoU from the type III secretion system is an important modulator of gene expression in lung epithelial cells in response to Pseudomonas aeruginosa infection. Infect Immun. 2003; 71(10):6035-44. PMC: 201109. DOI: 10.1128/IAI.71.10.6035-6044.2003. View

3.
Kugadas A, Geddes-McAlister J, Guy E, DiGiandomenico A, Sykes D, Mansour M . Frontline Science: Employing enzymatic treatment options for management of ocular biofilm-based infections. J Leukoc Biol. 2019; 105(6):1099-1110. PMC: 6618031. DOI: 10.1002/JLB.4HI0918-364RR. View

4.
Vance R, Rietsch A, Mekalanos J . Role of the type III secreted exoenzymes S, T, and Y in systemic spread of Pseudomonas aeruginosa PAO1 in vivo. Infect Immun. 2005; 73(3):1706-13. PMC: 1064930. DOI: 10.1128/IAI.73.3.1706-1713.2005. View

5.
Austin A, Lietman T, Rose-Nussbaumer J . Update on the Management of Infectious Keratitis. Ophthalmology. 2017; 124(11):1678-1689. PMC: 5710829. DOI: 10.1016/j.ophtha.2017.05.012. View