PREVENTION OF GENITAL HERPES SIMPLEX INFECTION

预防生殖器单纯疱疹感染

• 批准号: 3746577
• 负责人: S E STRAUS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746577
• 关键词: Herpesviridae vaccine; active immunization; acyclovir; clinical trials; disease /disorder prevention /control; dosage; drug design /synthesis /production; genital herpes; herpes simplex virus 1; herpes simplex virus 2; human subject; human therapy evaluation; immunomodulators; microorganism disease chemotherapy; relapse /recurrence; virus protein

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.

在完成了十多年的生殖器抗病毒治疗工作后， 疱疹，我们转向疾病预防和免疫疗法的研究。我们 完成了对新型重组HSV-2的开放式2年I期评估 在24名成年人中，一些人有和没有先前的糖蛋白D疫苗 HSV-1和/或2感染。在0， 1个月、2个月和12个月，与最小局部或全身性 反应.该疫苗在细胞内诱导了良好的一抗 免疫应答和增强的预先存在的体液和细胞应答 显著我们研究了以前未感染的抗体和T细胞 受试者，并表明抗体和细胞的gD 2表位 生殖器疱疹的症状有哪些？的基础上 这些优秀的反应，我们招募患者复发性生殖器 与美国卫生部合作，将疱疹纳入安慰剂对照疫苗试验 华盛顿大学。目标是确定是否 免疫力导致复发频率降低。研究完成后，我们 记录了98名受试者中，那些接受明矾中gD 2疫苗的受试者 复发率比仅接受明矾的患者低1/4 - 1/3。 这是有史以来第一次证明免疫疗法有效性的试验 慢性病毒感染然而，疾病改善率 低于预期的阿昔洛韦抑制治疗，所以我们 开始了一项剂量探索研究和一项使用gD 2联合 脂质佐剂MF 59中的gB 2。这项工作于1993财政年度完成。基于 我们启动了2项进一步的对照试验，一项是免疫治疗， 另一种是预防。到目前为止，已有110多名患者接种了疫苗， 一直到1995年。