PREVENTION OF GENITAL HERPES SIMPLEX INFECTION

完成了十多年的生殖器抗病毒治疗工作 关于疱疹，我们转向了疾病预防和免疫疗法的研究。 我们完成了对一种新的重组HSV-2的开放2年阶段1评估 24名成人明矾中的糖蛋白D疫苗，其中一些人之前有过或没有过 单纯疱疹病毒1型和/或2型感染。接种30微克或100微克疫苗的地点为 0个月、1个月、2个月和12个月，与最小的局部或全身相关 反应。该疫苗在细胞内诱导产生优良的一抗。 免疫反应和增强的先前存在的体液和细胞反应 意义重大。我们研究了以前的抗体和T细胞 未感染的受试者和显示GD2表位的抗体 和生殖器疱疹患者的细胞识别相对应。在……上面 这些出色反应的基础是我们招募的患者 将复发性生殖器疱疹纳入安慰剂对照疫苗试验 与华盛顿大学的合作。我们的目标是 确定增强的免疫力是否会降低复发的频率。 在完成研究后，我们记录了98名受试者，那些 在明矾中接种GD2疫苗后复发率降低1/4-1/3 而不是那些只接受明矾的人。这是第一次证明 在慢性病毒感染的免疫治疗中的疗效。收费率 然而，疾病的改善比预期的要低 阿昔洛韦抑制疗法，因此我们开始了一项剂量寻找研究和 GD2与GB2联合应用于脂类佐剂MF59的疗效研究。 这项工作已于1993财政年度完成。基于我们发起的数据，我们进一步 对照试验，一个用于免疫治疗，另一个用于预防。我们 完成免疫疗法试验的登记，在该试验中，患者 分别于0、2、12、14个月接种GB2/g02/MFSG疫苗，并随访 大鼠复发和严重程度18个月。这项研究将于 1995年10月。我们还完成了一项多中心研究 GB2/GD2/MF59用于预防生殖器疱疹。

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 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. We completed enrollment of the immunotherapy trial in which patients are vaccinated with gB2/g02/MFSG at 0, 2, 12, and 14 months and followed for recurrence of rats and severity for 18 months. The study will close in October 1995. We also completed enrollment of a multicenter study of gB2/gD2/MF59 for prevention of genital herpes.