Prevention of Herpes Simplex Virus Induced Stromal Keratitis by a Glycoprotein B-Specific Monoclonal Antibody

作者: Adalbert Krawczyk , Miriam Dirks , Maren Kasper , Anna Buch , Ulf Dittmer

DOI: 10.1371/JOURNAL.PONE.0116800

关键词:

摘要: The increasing incidence of acyclovir (ACV) and multidrug-resistant strains in patients with corneal HSV-1 infections leading to Herpetic Stromal Keratitis (HSK) is a major health problem industrialized countries often results blindness. To overcome this obstacle, we have previously developed an HSV-gB-specific monoclonal antibody (mAb 2c) that proved be highly protective immunodeficient NOD/SCID-mice towards genital infections. In the present study, examined effectivity mAb 2c preventing immunopathological disease HSK BALB/c mouse model. Therefore, mice were inoculated strain KOS on scarified cornea induce subsequently either systemically or topically treated 2c. Systemic treatment was performed by intravenous administration 24 h prior infection (pre-exposure prophylaxis) 24, 40, 56 hours after (post-exposure immunotherapy). Topical periodical inoculations (5 times per day) antibody-containing eye drops as control, starting at post infection. markedly reduced viral loads site completely protected from developing HSK. antiviral equally effective. had no improving effect severity conclusion, our data demonstrate excellent drug for HSV-infections prevention Moreover, humanized counterpart hu2c) effective protecting HSV-induced when compared parental antibody. These warrant future development novel approach humans.

参考文章(58)
A de Ramus, M Allansmith, D Maurice, The dynamics of IgG in the cornea. Investigative Ophthalmology & Visual Science. ,vol. 18, pp. 947- 955 ,(1979)
B T Rouse, H S Larsen, R G Russell, M P Nasisse, Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis. Investigative Ophthalmology & Visual Science. ,vol. 25, pp. 938- 944 ,(1984)
B T Rouse, M G Niemialtowski, Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis. Journal of Immunology. ,vol. 149, pp. 3035- 3039 ,(1992)
Q Tang, R L Hendricks, W Chen, Proinflammatory functions of IL-2 in herpes simplex virus corneal infection. Journal of Immunology. ,vol. 158, pp. 1275- 1283 ,(1997)
Anna M. Eis-Hübinger, Klaudia Mohr, Karl E. Schneweis, Different mechanisms of protection by monoclonal and polyclonal antibodies during the course of herpes simplex virus infection. Intervirology. ,vol. 32, pp. 351- 360 ,(1991) , 10.1159/000150219
Asim V. Farooq, Deepak Shukla, Herpes Simplex Epithelial and Stromal Keratitis: An Epidemiologic Update Survey of Ophthalmology. ,vol. 57, pp. 448- 462 ,(2012) , 10.1016/J.SURVOPHTHAL.2012.01.005