一种可减少复发性单纯疱疹病毒1型角膜疾病的治疗性疫苗。

A therapeutic vaccine that reduces recurrent herpes simplex virus type 1 corneal disease.

作者信息

Nesburn A B, Burke R L, Ghiasi H, Slanina S M, Wechsler S L

机构信息

Ophthalmology Research, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA.

出版信息

Invest Ophthalmol Vis Sci. 1998 Jun;39(7):1163-70.

PMID:9620075

Abstract

PURPOSE

To investigate the therapeutic efficacy of periocular vaccination with herpes simplex virus (HSV) recombinant glycoprotein D from HSV-1 (gD1) or HSV-2 (gD2) in decreasing HSV-induced recurrent dendritic keratitis and HSV-induced recurrent ocular shedding in rabbits latently infected with HSV-1.

METHODS

Rabbits latently infected with HSV-1 were vaccinated periocularly (by subconjunctival injection) with gD1 and adjuvant, gD2 and adjuvant, or adjuvant alone. Eyes were examined daily for 49 days for recurrent herpetic keratitis and for recurrent infectious HSV-1 shedding.

RESULTS

In both vaccinated groups, a significantly decreased number of eyes exhibited recurrences of herpetic keratitis compared with recurrences in adjuvant-treated control eyes (gD1 group, 27/1372, [2%]; gD2 group, 24/1274, [2%]; and control, 54/1274 [4%]; P < 0.005). Eyes in the gD1-vaccinated group (44/1308 [3.4%]; P = 0.01), but not those in the gD2-vaccinated group (71/1274 [5.6%]; P = 0.93), had significantly decreased viral shedding (positive cultures compared with total cultures) compared with eyes in the adjuvant-treated control group (69 of 1275 [5.4%]).

CONCLUSIONS

Recurrent HSV-1 corneal disease was significantly reduced by therapeutic local periocular vaccination. The vaccine may be more efficacious against HSV-1-induced recurrent corneal disease than against recurrent HSV-1 ocular shedding. Its efficacy against corneal disease appeared to be longer lasting than its efficacy against recurrent spontaneous shedding. The heterotypic gD2 vaccine was as efficacious as the homotypic gD1 vaccine against recurrent corneal disease, whereas the homotypic vaccine was much more efficacious than the heterotypic vaccine against recurrent HSV-1 shedding. This is the first report in any animal model of a successful therapeutic vaccine against recurrent HSV-1-induced corneal disease. These results support the concept that development of a therapeutic vaccine for ocular HSV-1 recurrence in humans may be possible.

摘要

目的

研究用来自1型单纯疱疹病毒（HSV-1）的重组糖蛋白D（gD1）或2型单纯疱疹病毒（HSV-2）的重组糖蛋白D（gD2）进行眼周接种疫苗，在降低HSV诱导的复发性树枝状角膜炎以及降低HSV-1潜伏感染兔的HSV诱导的复发性眼部病毒脱落方面的治疗效果。

方法

对HSV-1潜伏感染的兔通过结膜下注射眼周接种gD1与佐剂、gD2与佐剂或单独的佐剂。每天检查眼睛49天，观察复发性疱疹性角膜炎和复发性感染性HSV-1脱落情况。

结果

与佐剂治疗的对照眼相比，两个接种疫苗组中出现疱疹性角膜炎复发的眼睛数量均显著减少（gD1组，27/1372，[2%]；gD2组，24/1274，[2%]；对照组，54/1274 [4%]；P<0.005）。与佐剂治疗的对照组眼睛（1275只中的69只[5.4%]）相比，gD1接种疫苗组的眼睛（44/1308 [3.4%]；P = 0.01）病毒脱落显著减少（阳性培养物与总培养物相比），而gD2接种疫苗组的眼睛（71/1274 [5.6%]；P = 0.93）则没有。

结论

通过治疗性局部眼周接种疫苗，HSV-1复发性角膜疾病显著减少。该疫苗对HSV-1诱导的复发性角膜疾病可能比对复发性HSV-1眼部病毒脱落更有效。其对角膜疾病的疗效似乎比对复发性自发病毒脱落的疗效持续时间更长。异型gD2疫苗在预防复发性角膜疾病方面与同型gD1疫苗一样有效，而在预防复发性HSV-1病毒脱落方面，同型疫苗比异型疫苗更有效。这是在任何动物模型中首次成功报道针对复发性HSV-1诱导的角膜疾病的治疗性疫苗。这些结果支持了在人类中开发用于眼部HSV-1复发的治疗性疫苗可能可行的概念。