Experimental Gonococcal Vaccine

摘要 生殖道感染淋病奈瑟菌(淋病)不会导致特定的保护性状态 免疫力是可以反复获得的。尽管采取了公共卫生措施，但这种疾病仍在以 频率高得令人无法接受；没有针对它的疫苗，甚至对最新一代的 抗生素不断涌现。最近的研究结果表明，淋病奈瑟菌能破坏人体的免疫功能。 系统为了自身的利益，通过激发它可以生存的先天反应和抑制特定的适应性 将会消除它的回应。然而，这种诱导的免疫抑制可以通过治疗逆转。 这有效地改变了对淋病奈瑟菌的免疫反应。已经建立了原则证明 用于预防生殖器淋球菌感染的新策略，使用已被接受的小鼠模型 作为目前唯一可用的动物模型。目前的疫苗原型GvaX12®(一种组合疫苗 我们的专利缓释纳米粒白介素12和淋球菌外膜制剂的研制 膜泡)诱导抗淋球菌T细胞和抗体反应，并产生保护作用 同源和异源菌株最多6个月。在此第二阶段应用程序中，我们将定义、优化 并验证了包括路线在内的疫苗接种方案，目的是鼻腔给药。我们将确定 对自然产生的不同淋病奈瑟菌株的交叉保护基础，并开始初步 药代动力学和毒理学研究为后续的非人类毒理学测试做准备 灵长类动物。与临床前数据一起，毒理学结果和未来计划将被纳入简报中 将在C类会议请求中提交给FDA的一揽子计划。

ABSTRACT Genital tract infection with Neisseria gonorrhoeae (gonorrhea) does not induce a state of specific protective immunity and it can be acquired repeatedly. Despite public health measures, the disease persists at an unacceptably high frequency; there is no vaccine against it, and resistance even to the latest generations of antibiotics continues to emerge. Recent findings have revealed that N. gonorrhoeae subverts the immune system for its own benefit by eliciting innate responses that it can survive and by suppressing specific adaptive responses that would eliminate it. However, this induced immunosuppression can be reversed by treatments that effectively redirect the immune response against N. gonorrhoeae. Proof-of-principle has been established for a novel strategy of prophylaxis against genital gonococcal infection using a mouse model that is accepted as the only currently available animal model. The current vaccine prototype, GvaX12® (a combinatorial formulation of our proprietary sustained-release nanoparticulate interleukin-12 and gonococcal outer membrane vesicles) induces anti-gonococcal T-cell and antibody responses, and generates protection against homologous and heterologous strains for up to 6 months. In this Phase II application, we will define, optimize, and validate a vaccination regimen including route, aiming for intranasal administration. We will determine the basis of cross-protection against diverse strains of naturally occurring N. gonorrhoeae, and begin preliminary pharmacokinetics and toxicology studies in preparation for subsequent toxicological testing in nonhuman primates. Along with the preclinical data, toxicology results and future plans will be incorporated into a briefing package that will be submitted to the FDA in a request for a Type C Meeting.