An R2 non-neuroinvasive herpes simplex virus type 2 vaccine

项目总结 对单纯疱疹病毒(HSV)疫苗的需求尚未得到满足。我们建议 基于我们的R2技术平台开发HSV-2减毒活疫苗。R2 疫苗在动物模型中显示出前所未有的安全性和有效性，并提供了 抗原性优于亚单位/信使核糖核酸和单轮疫苗设计。R2疫苗 也是第一种没有神经侵袭的甲型疱疹病毒减毒活疫苗 潜在性的，因此不能在神经中建立终身感染 系统。在这一快速通道STTR应用的第一阶段，我们建议：(I)产生HSV- 2个低传代临床分离株的自切感染性克隆，(Ii)使用该克隆 生产HSV-2R2重组病毒，以及(Iii)通过以下方式鉴定R2疫苗的培养特性 与我们现有的HSV-1R2候选疫苗站在一边。在第二阶段，HSV-2R2疫苗 将在小鼠和豚鼠身上进行安全性、免疫原性和有效性测试。这部作品 将为将产品开发推进到临床试验提供基础。

PROJECT SUMMARY There is an unmet need for a herpes simplex virus (HSV) vaccine. We propose to develop a live-attenuated HSV-2 vaccine based on our R2 technology platform. R2 vaccines show unprecedented safety and efficacy in animal models, and offer antigenicity superior to subunit/mRNA and single-round vaccine designs. R2 vaccines are also the first live-attenuated alphaherpesvirus vaccines that lack neuroinvasive potential, and thereby are incapable of establishing life-long infections in the nervous system. In phase I of this fast-track STTR application, we propose to: (i) produce a HSV- 2 self-excising infectious clone of a low-passage clinical isolate, (ii) use the clone to produce a HSV-2 R2 recombinant, and (iii) characterize the R2 vaccine in culture side by side with our existing HSV-1 R2 vaccine candidate. In phase II, the HSV-2 R2 vaccine will be tested for safety, immunogenicity, and efficacy in mice and guinea pigs. This work will provide the foundation to advance product development to clinical trials.