Heiligenhaus A, Wells P A, Foster C S
Department of Ophthalmology, University of Essen, Germany.
Eye (Lond). 1995;9 ( Pt 1):89-95. doi: 10.1038/eye.1995.14.
The authors tested the protective efficacy of, and the immune response to, immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine model of herpes stromal keratitis (HSK). HSV-1 susceptible A/J mice were immunised subcutaneously with a peptide corresponding to the N-terminal epitope gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were compared for their protective potency, their ability to prevent the establishment of latency in the trigeminal ganglion, and their effect on the immune system. Low dosages (31 micrograms) of gD(5-23) protected against encephalitis and HSK. Protective efficacy was higher when gD(5-23) was coupled to the carrier protein keyhole limpet haemocyanin (KLH) and was emulsified with adjuvant. Latent infection was found in all control mice but in only 50-75% of immunised mice. The most potent protection was correlated with anti-HSV-1 neutralising antibodies of IgG1 and IgG2a isotypes, but free gD(5-23) protected in the absence of anti-HSV-1 antibodies. Our results suggest that immunisation with gD(5-23) stimulates both humoral and cellular immune mechanisms which protect against HSV-1 keratitis.
作者在疱疹性基质性角膜炎(HSK)小鼠模型中测试了用单纯疱疹病毒1型(HSV-1)糖蛋白D(gD)的合成肽进行免疫接种的保护效力及免疫反应。在角膜HSV-1攻击前,对HSV-1易感的A/J小鼠皮下接种对应于N端表位gD(5-23)的肽。比较了不同免疫方案在保护效力、预防三叉神经节潜伏感染的能力以及对免疫系统的影响方面的差异。低剂量(31微克)的gD(5-23)可预防脑炎和HSK。当gD(5-23)与载体蛋白钥孔戚血蓝蛋白(KLH)偶联并用佐剂乳化时,保护效力更高。在所有对照小鼠中均发现潜伏感染,但在仅50%-75%的免疫小鼠中发现潜伏感染。最有效的保护作用与IgG1和IgG2a同种型的抗HSV-1中和抗体相关,但游离的gD(5-23)在没有抗HSV-1抗体的情况下也具有保护作用。我们的结果表明,用gD(5-23)进行免疫接种可刺激体液免疫和细胞免疫机制,从而预防HSV-1角膜炎。