Ocular distribution, spectrum of activity, and in vivo viral neutralization of a fully humanized anti-herpes simplex virus IgG Fab fragment following topical application.

Détails

ID Serval
serval:BIB_1F19F7E23E71
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ocular distribution, spectrum of activity, and in vivo viral neutralization of a fully humanized anti-herpes simplex virus IgG Fab fragment following topical application.
Périodique
Antimicrobial Agents and Chemotherapy
Auteur(s)
Berdugo M., Larsen I.V., Abadie C., Deloche C., Kowalczuk L., Touchard E., Dubielzig R., Brandt C.R., Behar-Cohen F., Combette J.M.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
56
Numéro
3
Pages
1390-1402
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Herpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC(50) and MEC(90), respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. The in vivo efficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, but not as much as with trifluridine (TFT). AC-8 treatment reduced viral titers but less than trifluridine. AC-8 did not display any toxicity to the cornea or other structures in the eye. In summary, topical instillation of an anti-HSV FAb can be used on both intact and ulcerated corneas. It is well tolerated and does not alter reepithelialization. Further studies to improve the antiviral effect are needed for AC-8 to be considered for therapeutic use.
Mots-clé
Administration, Topical, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Humanized/administration & dosage, Antibodies, Monoclonal, Humanized/immunology, Antibodies, Viral/immunology, Antiviral Agents/administration & dosage, Antiviral Agents/immunology, Drug Resistance, Viral, Epithelium, Corneal/metabolism, Eye/drug effects, Eye/metabolism, Herpesvirus 1, Human/immunology, Humans, Immunoglobulin Fab Fragments/administration & dosage, Immunoglobulin Fab Fragments/immunology, Inhibitory Concentration 50, Keratitis, Herpetic/drug therapy, Keratitis, Herpetic/virology, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Neuroglia/metabolism, Rats, Retina/metabolism, Stromal Cells/metabolism, Tissue Distribution, Trifluridine/administration & dosage
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/08/2013 15:26
Dernière modification de la notice
20/08/2019 12:55
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