PREVENTION OF GENITAL HERPES SIMPLEX INFECTION

完成了十多年的生殖器抗病毒治疗工作 疱疹，我们转向疾病预防和免疫治疗的研究。我们 完成了新重组 HSV-2 的开放式 2 年 1 期评估 对 24 名成人进行明矾中的糖蛋白 D 疫苗接种，其中一些人之前接受过或未接受过疫苗接种 HSV-1 和/或 2 感染。 0时接种30微克或100微克的疫苗， 1、2 和 12 个月，与最小的局部或全身相关 反应。该疫苗在细胞中诱导出优异的一抗 免疫反应和增强已有的体液和细胞反应 显着。我们研究了之前未感染的抗体和 T 细胞 受试者并表明抗体和细胞的 gD2 表位 识别对应于生殖器疱疹患者。基于 这些出色的反应让我们招募了患有复发性生殖器疾病的患者 与疱疹病毒合作进行安慰剂对照疫苗试验 华盛顿大学。目标是确定是否增强 免疫力会降低复发率。完成研究后我们 记录显示，在 98 名受试者中，接受明矾 gD2 疫苗的受试者 与单独接受明矾治疗的患者相比，复发率减少了 1/4 - 1/3。 这是有史以来第一个证明免疫疗法疗效的试验 慢性病毒感染。然而，疾病改善率 低于阿昔洛韦抑制治疗的预期，因此我们 开始使用 gD2 联合进行剂量寻求研究和功效研究 脂质佐剂 MF59 中的 gB2。该项目于 1993 财年完成。基于 根据数据，我们启动了两项进一步的对照试验，一项用于免疫疗法， 其他用于预防。迄今为止已有 110 多名患者接种了疫苗，并将继续接种 一直延续到1995年。

Having completed over a decade of work on antiviral treatment of genital herpes, we turned to studies of disease prevention and immunotherapy. We completed an open 2 year phase 1 assessment of a new recombinant HSV-2 glycoprotein D vaccine in alum in 24 adults, some with and without prior HSV-1 and/or 2 infection. Vaccinations of 30 ug or 100 ug were given at 0, 1, 2, and 12 months and were associated with minimal local or systemic reactions. The vaccine induced excellent primary antibody in cellular immune responses and augmented preexisting humoral and cellular responses significantly. We studied antibody and T cells from previously uninfected subjects and showed that the gD2 epitopes that the antibody and cell recognize correspond to those in genital herpes patients. On the basis of these excellent responses we enrolled patients with recurrent genital herpes into a placebo-controlled vaccine trial in collaboration with the University of Washington. The goal was to determine whether boosted immunity leads to less frequent recurrences. Upon completing the study we documented that of 98 subjects, those who received the gD2 vaccine in alum experienced 1/4 - 1/3 fewer recurrences than those receiving alum alone. This is the first ever trial to demonstrate efficacy in the immunotherapy of a chronic viral infection. Rates of disease improvement, though, were lower than would be expected with acyclovir suppressive therapy so we began a dose seeking study and an efficacy study using gD2 combined with gB2 in a lipid adjuvant MF59. This was completed in FY1993. Based on the data we initiated 2 further controlled trials, one for immunotherapy, the other for prophylaxis. Over 110 patients were vaccinated thus far and will be followed until 1995.