RATIONAL DESIGN OF A LIVE, ATTENUATED HSV2 VACCINE

描述：（改编自申请人摘要）单纯疱疹病毒 感染了五分之一的美国人 生殖器疱疹的症状有哪些 生殖器的复发性水泡或溃疡性损伤。 活动性病变 是艾滋病毒性传播的一个危险因素。 HSV可以传播 在原发性或复发性感染期间，无论临床是否 目前存在各种表现，这使许多未出生的婴儿处于危险之中。 新生儿疱疹感染通常很严重，死亡率很高 存活者的死亡率和严重的神经功能障碍。 当前没有任何 有许可的疫苗可用于预防HSV疾病， 证明佐剂化亚单位疫苗的效力的试验失败了。 一个 有效疫苗将减少HSV的传播， 新生儿疾病，降低与预防相关的并发症风险 剖腹产可能减少艾滋病毒的传播， 大大降低了相关的医疗费用。 这个实验 第一阶段SBIR建议利用最新进展， 合理设计的HSV-2重组体。 在以前工作的基础上， 减毒HSV-1重组体，它们已经去除了全部或部分的 HSV-2内部反向重复序列。 此外，他们的临床前研究 与减毒HSV-2重组体的研究表明， 方法产生保护性免疫水平。 一种安全的，免疫原性 将选择减毒活疫苗候选物， 发展 本研究的具体目标是：1）创造 具有内部修饰的重组HSV-2疫苗株 重复序列区，2）确定内部重复序列中必需的区域 用于神经毒力，和3）选择神经减毒的遗传稳定的 用于疫苗开发的病毒。 拟议商业应用：不可用

DESCRIPTION: (Adapted from the applicant's abstract) Herpes simplex virus infects one in five Americans. Genital herpes is characterized by recurrent vesicular or ulcerative lesions of the genitals. Active lesions are a risk factor for sexual transmission of HIV. HSV can be transmitted during primary or recurrent infection, regardless of whether clinical manifestations are present, which puts many unborn children at risk. Neonatal herpetic infections are frequently severe, with a high mortality rate and substantial neurologic impairment in survivors. Currently, no licensed vaccine is available to prevent HSV disease, and recent attempts to demonstrate efficacy of adjuvanted subunit vaccines have failed. An efficacious vaccine would reduce transmission of HSV and consequences of neonatal disease, lower the complication risk associated with preventative cesarean deliveries potentially reduce transmission of HIV and significantly lower associated healthcare costs. The experiments in this phase 1 SBIR proposal utilize recent advances to generate a set of rationally designed HSV-2 recombinants. Building upon previous work with attenuated HSV-1 recombinants, they have removed all, or part of, the internal inverted repeat of HSV-2. In addition, their preclinical studies with live attenuated HSV-2 recombinants have demonstrated that this approach produces protective levels of immunity. A safe, immunogenic live, attenuated vaccine candidate will be selected for further development. Specific aims of the proposed research are 1) create recombinant HSV-2 vaccine strains with modifications of the internal repeat region, 2) identify the region in the internal repeats essential for neurovirulence, and 3) select a neuroattenuated genetically stable virus for vaccine development. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE