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通过针对糖蛋白D上不连续和连续表位的单克隆抗体预防疱疹性角膜炎。

Prevention of herpes keratitis by monoclonal antibodies specific for discontinuous and continuous epitopes on glycoprotein D.

作者信息

Lousch R N, Staats H, Oakes J E, Cohen G H, Eisenberg R J

机构信息

Department of Microbiology/Immunology, University of South Alabama, Mobile 36688.

出版信息

Invest Ophthalmol Vis Sci. 1991 Sep;32(10):2735-40.

PMID:1716618
Abstract

Seven monoclonal antibodies (mAb) specific for defined discontinuous and continuous epitopes on glycoprotein D of herpes simplex virus type 1 (HSV-1) were surveyed for their capacity to protect against virus-induced corneal disease in a murine ocular infection model. A known amount of purified mAb was transferred passively to BALB/c mice 24 hr after topical infection with HSV-1 on their scarified corneas. At high doses (50-136 micrograms), all seven mAbs protected against the development of persistent necrotizing stromal keratitis. Significant protection was also observed at low doses (20 micrograms) with two mAbs to discontinuous epitopes and two mAbs to continuous epitopes. Selected high-dose mAbs also were able to reduce the severity of blepharitis. These results indicated that at least seven different antigenic sites on glycoprotein D can serve as targets for effective antibody therapy in the murine model of HSV-1 ocular infection.

摘要

在小鼠眼部感染模型中,对七种针对单纯疱疹病毒1型(HSV-1)糖蛋白D上特定不连续和连续表位的单克隆抗体(mAb)进行了研究,以考察它们预防病毒诱导的角膜疾病的能力。在经划痕处理的角膜上局部感染HSV-1 24小时后,将已知量的纯化单克隆抗体被动转移至BALB/c小鼠体内。在高剂量(50 - 136微克)时,所有七种单克隆抗体都能预防持续性坏死性基质角膜炎的发展。在低剂量(20微克)时,两种针对不连续表位的单克隆抗体和两种针对连续表位的单克隆抗体也观察到了显著的保护作用。选定的高剂量单克隆抗体还能够减轻睑缘炎的严重程度。这些结果表明,在HSV-1眼部感染的小鼠模型中,糖蛋白D上至少七个不同的抗原位点可作为有效抗体治疗的靶点。

相似文献

1
Prevention of herpes keratitis by monoclonal antibodies specific for discontinuous and continuous epitopes on glycoprotein D.通过针对糖蛋白D上不连续和连续表位的单克隆抗体预防疱疹性角膜炎。
Invest Ophthalmol Vis Sci. 1991 Sep;32(10):2735-40.
2
Passive transfer of anti-herpes simplex virus type 2 monoclonal and polyclonal antibodies protect against herpes simplex virus type 1-induced but not herpes simplex virus type 2-induced stromal keratitis.抗单纯疱疹病毒2型单克隆抗体和多克隆抗体的被动转移可预防单纯疱疹病毒1型诱发的基质性角膜炎,但不能预防单纯疱疹病毒2型诱发的基质性角膜炎。
Invest Ophthalmol Vis Sci. 1993 Jul;34(8):2460-8.
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Monoclonal antibodies to the distinct antigenic sites on glycoproteins C and B and their protective abilities in herpes simplex virus infection.针对糖蛋白C和B上不同抗原位点的单克隆抗体及其在单纯疱疹病毒感染中的保护能力。
Acta Virol. 1997 Feb;41(1):5-12.
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Protection against herpes simplex virus-induced eye disease after vaccination with seven individually expressed herpes simplex virus 1 glycoproteins.用七种单独表达的单纯疱疹病毒1型糖蛋白进行疫苗接种后对单纯疱疹病毒引起的眼部疾病的防护作用。
Invest Ophthalmol Vis Sci. 1995 Jun;36(7):1352-60.
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Herpes simplex virus glycoprotein D. Protective immunity against murine herpetic keratitis.
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Human natural killer cell recognition of herpes simplex virus type 1 glycoproteins: specificity analysis with the use of monoclonal antibodies and antigenic variants.人类自然杀伤细胞对1型单纯疱疹病毒糖蛋白的识别:使用单克隆抗体和抗原变体进行特异性分析。
J Immunol. 1984 Oct;133(4):2206-14.
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Protective immunity against ocular herpes infection and disease induced by highly immunogenic self-adjuvanting glycoprotein D lipopeptide vaccines.由高免疫原性自佐剂糖蛋白D脂肽疫苗诱导的针对眼部疱疹感染和疾病的保护性免疫。
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A related epitope is consistently present on glycoprotein C of herpes simplex virus type 1 and 2.一个相关表位始终存在于1型和2型单纯疱疹病毒的糖蛋白C上。
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Human herpesvirus-6 glycoprotein H and L homologs are components of the gp100 complex and the gH external domain is the target for neutralizing monoclonal antibodies.人类疱疹病毒6型糖蛋白H和L同源物是gp100复合体的组成成分,且gH胞外结构域是中和性单克隆抗体的作用靶点。
Virology. 1993 Nov;197(1):12-22. doi: 10.1006/viro.1993.1562.
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Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica.登革2型病毒包膜糖蛋白的单克隆抗体定位,牙买加。
Virology. 1998 Jul 5;246(2):317-28. doi: 10.1006/viro.1998.9200.

引用本文的文献

1
Monoclonal Antibodies, Derived from Humans Vaccinated with the RV144 HIV Vaccine Containing the HVEM Binding Domain of Herpes Simplex Virus (HSV) Glycoprotein D, Neutralize HSV Infection, Mediate Antibody-Dependent Cellular Cytotoxicity, and Protect Mice from Ocular Challenge with HSV-1.源自接种含单纯疱疹病毒(HSV)糖蛋白D的HVEM结合域的RV144 HIV疫苗的人类的单克隆抗体,可中和HSV感染,介导抗体依赖性细胞毒性,并保护小鼠免受HSV - 1的眼部攻击。
J Virol. 2017 Sep 12;91(19). doi: 10.1128/JVI.00411-17. Print 2017 Oct 1.
2
Easy and reliable double-immunogold labelling of herpes simplex virus type-1 infected cells using primary monoclonal antibodies and studied by cryosection electron microscopy.使用一抗对单纯疱疹病毒1型感染细胞进行简单可靠的双免疫金标记,并通过冷冻切片电子显微镜进行研究。
Histochem J. 1999 Aug;31(8):525-33. doi: 10.1023/a:1003840006848.
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Localization of a passively transferred human recombinant monoclonal antibody to herpes simplex virus glycoprotein D to infected nerve fibers and sensory neurons in vivo.被动转移的人重组单克隆抗体针对单纯疱疹病毒糖蛋白D在体内对感染神经纤维和感觉神经元的定位。
J Virol. 1999 Oct;73(10):8817-23. doi: 10.1128/JVI.73.10.8817-8823.1999.
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Protective antibody therapy is associated with reduced chemokine transcripts in herpes simplex virus type 1 corneal infection.在单纯疱疹病毒1型角膜感染中,保护性抗体疗法与趋化因子转录物减少相关。
J Virol. 1996 Feb;70(2):1277-81. doi: 10.1128/JVI.70.2.1277-1281.1996.