Ghiasi H, Perng G C, Nesburn A B, Wechsler S L
Ophthalmology Research, Cedars-Sinai Burn and Allen Research Institute, CSMC-Davis Bldg., Room 5072, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
Virus Res. 2000 Jul;68(2):137-44. doi: 10.1016/s0168-1702(00)00165-9.
We previously reported that vaccination of BALB/c mice with the baculovirus expressed HSV-1 glycoprotein K (gK) or passive transfer of gK purified IgG to naive BALB/c mice causes severe exacerbation of HSV-1 induced corneal scarring following ocular challenge. In addition, a productive chronic infection, rather than a latent infection, is found in most trigeminal ganglia. These phenomena are accompanied by a very high T(H)1+T(H)2 response in the eye (Ghiasi, H., Cai, S., Nesburn, A.B., Wechsler, S.L., 1996. Vaccination with herpes simplex virus type 1 glycoprotein K impairs clearance of virus from the trigeminal ganglia resulting in chronic infection. Virology 224, 330-333; Ghiasi, H., Cai, S., Slanina, S., Nesburn, A. B., Wechsler, S.L., 1997. Nonneutralizing antibody against the glycoprotein K of herpes simplex virus type-1 exacerbates herpes simplex virus type-1-induced corneal scarring in various virus-mouse strain combinations. Invest. Ophthalmol. Vis. Sci. 38, 1213-1221; Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn, A.B., Wechsler, S.L., 1999. Vaccination with different HSV-1 glycoproteins induces different patterns of ocular cytokine responses following HSV-1 challenge of vaccinated mice. Vaccine 17, 2576-2582). In the studies reported here, we investigated the hypothesis that anti-gK serum produces antibody-dependent enhancement (ADE) of ocular HSV-1 infection. We found that gK vaccinated mice had significantly higher HSV-1 titers in their eyes than gD or mock-vaccinated mice and that anti-gK sera enhanced HSV-1 infection in the macrophage cell line U937. In addition, passive transfer of anti-gK sera to naive mice 24 h prior to ocular HSV-1 challenge also increased viral replication. These results were consistent with ADE of HSV-1 by sera to gK. This suggests that the severely exacerbated corneal disease seen following HSV-1 ocular challenge of gK vaccinated mice is a result of ADE. The ability of gK sera to cause harmful ADE may impact HSV-1 vaccine development.
我们之前报道过，用杆状病毒表达的单纯疱疹病毒1型糖蛋白K（gK）对BALB/c小鼠进行疫苗接种，或将纯化的gK IgG被动转移至未接触过病毒的BALB/c小鼠，在眼部感染单纯疱疹病毒1型后，会导致角膜瘢痕形成严重加剧。此外，在大多数三叉神经节中发现的是活跃的慢性感染，而非潜伏感染。这些现象伴随着眼部非常高的辅助性T细胞1（Th1）+辅助性T细胞2（Th2）反应（吉亚西，H.，蔡，S.，内斯本，A.B.，韦克斯勒，S.L.，1996年。用单纯疱疹病毒1型糖蛋白K进行疫苗接种会损害病毒从三叉神经节的清除，导致慢性感染。《病毒学》224卷，第330 - 333页；吉亚西，H.，蔡，S.，斯拉尼纳，S.，内斯本，A.B.，韦克斯勒，S.L.，1997年。针对单纯疱疹病毒1型糖蛋白K的非中和抗体在各种病毒 - 小鼠品系组合中会加剧单纯疱疹病毒1型诱导的角膜瘢痕形成。《Invest. Ophthalmol. Vis. Sci.》38卷，第1213 - 1221页；吉亚西，H.，霍夫曼，F.M.，蔡，S.，彭，G.C.，内斯本，A.B.，韦克斯勒，S.L.，1999年。用不同的单纯疱疹病毒1型糖蛋白进行疫苗接种，在接种疫苗的小鼠受到单纯疱疹病毒1型攻击后，会诱导出不同模式的眼部细胞因子反应。《疫苗》17卷，第2576 - 2582页）。在本报告的研究中，我们研究了抗gK血清产生眼部单纯疱疹病毒1型感染的抗体依赖性增强（ADE）这一假说。我们发现，接种gK疫苗的小鼠眼中的单纯疱疹病毒1型滴度显著高于接种gD或模拟疫苗的小鼠，并且抗gK血清增强了巨噬细胞系U937中的单纯疱疹病毒1型感染。此外，在眼部单纯疱疹病毒1型攻击前24小时，将抗gK血清被动转移至未接触过病毒的小鼠也增加了病毒复制。这些结果与血清对gK产生的单纯疱疹病毒1型ADE一致。这表明，在接种gK疫苗的小鼠受到单纯疱疹病毒1型眼部攻击后出现的严重加剧的角膜疾病是ADE的结果。gK血清导致有害ADE的能力可能会影响单纯疱疹病毒1型疫苗的研发。
