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用抗单纯疱疹病毒单克隆抗体治疗实验性单纯疱疹病毒性角膜炎的体内观察及电子显微镜检查

In vivo observations and electron microscopy of treatment of experimental HSV keratitis with anti-HSV monoclonal antibodies.

作者信息

Yu J, Zhang Y, Zhang D

机构信息

Department of Ophthalmology, Tangdu Hospital Fourth Military Medical University, Xian, China.

出版信息

Yan Ke Xue Bao. 1996 Sep;12(3):145-50.

PMID:9639841
Abstract

PURPOSE

To study the antiviral activity of monoclonal antibodies (McAb) in vivo and identify their effects on experimental herpetic keratitis.

METHODS

Topical use of anti-HSV monoclonal glycoprotein antibodies was carried out on acute herpetic keratitis of rabbits infected by HSV-1 SM44. The application of the eye drops in each group was five times per day for 14 days by double-blind method. In vivo observation and electron microscopy were performed during the whole procedure. The anti-HSV McAb's solution was mixed up of five monoclonal antibodies with high neutrilization titers and/or high ADCC activity.

RESULTS

Compared with placebo-treated eyes, anti-HSV McAb treatment made statistically significant reduction of herpetic corneal epithelial lesion on rabbits from day 3 to day 14 postinnoculation (P < 0.01). Punctate and short dendritic lesion were the main patterns. The area of involvement was also limited. Electron microscopic analysis showed ultrastructural changes of herpetic corneal infection. The clumping of nuclear chromatin, swollon nuclei, reduction of microflament, rounding of epithelial cells were apparent in placebo-treated eyes. The advanced lesion of the viral infection was karyolysis, karyoklasis and disruption of cells in both scanning and transmission electron micrographes. The management of the McAb-treated eyes showed that the pathological involvements as mentioned above reduced remarkably.

CONCLUSION

Topical application of anti-HSV monoclonal antibodies produced marked antiviral effects in inhibiting the development of experimental herpetic keratitis in rabbits and in protecting the susceptible corneal cells. As a new biological product, the anti-HSV monoclonal antibodies may provide a new approach to the treatment of HSV keratits.

摘要

目的

研究单克隆抗体(McAb)在体内的抗病毒活性,并确定其对实验性疱疹性角膜炎的作用。

方法

对感染HSV-1 SM44的兔急性疱疹性角膜炎局部应用抗HSV单克隆糖蛋白抗体。采用双盲法,每组滴眼液每天滴眼5次,共14天。在整个过程中进行体内观察和电子显微镜检查。抗HSV McAb溶液由五种具有高中和效价和/或高ADCC活性的单克隆抗体混合而成。

结果

与安慰剂治疗的眼相比,抗HSV McAb治疗使接种后第3天至第14天兔的疱疹性角膜上皮病变有统计学意义的减少(P<0.01)。点状和短树枝状病变是主要类型。受累面积也有限。电子显微镜分析显示疱疹性角膜感染的超微结构变化。在安慰剂治疗的眼中,核染色质聚集、细胞核肿胀、微丝减少、上皮细胞变圆明显。在扫描和透射电子显微镜下,病毒感染的晚期病变为核溶解、核碎裂和细胞破坏。McAb治疗眼的情况显示,上述病理改变明显减轻。

结论

局部应用抗HSV单克隆抗体在抑制兔实验性疱疹性角膜炎的发展和保护易感角膜细胞方面产生了显著的抗病毒作用。作为一种新的生物制品,抗HSV单克隆抗体可能为HSV角膜炎的治疗提供一种新方法。

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