Experimental Gonococcal Vaccine

摘要 生殖道感染淋病奈瑟氏菌（淋病）不会诱导特异性保护性免疫状态。 免疫力，可以反复获得。尽管采取了公共卫生措施，但这种疾病仍在继续， 高得令人无法接受的频率;没有针对它的疫苗，甚至对最新一代的 抗生素不断涌现。最近的研究表明，N.淋病破坏免疫系统 系统为了自身的利益，通过引发先天反应，它可以生存，并通过抑制特定的适应性 可以消除它的反应。然而，这种诱导的免疫抑制可以通过治疗逆转 能有效地改变免疫反应的方向淋病原则证明已经确立 使用小鼠模型预防生殖器淋球菌感染的新策略， 作为目前唯一可用的动物模型。当前的疫苗原型GvaX 12 ®（组合疫苗） 我们专有的持续释放纳米颗粒白细胞介素-12和淋球菌外 膜囊泡）诱导抗淋球菌T细胞和抗体应答，并产生针对 同源和异源菌株长达6个月。在第二阶段的应用中，我们将定义，优化， 并验证包括途径的疫苗接种方案，目的是鼻内给药。康贝特人将以 交叉保护的基础上，对自然发生的N.淋病，并开始初步 为后续非人毒理学试验做准备的药代动力学和毒理学研究 灵长类动物沿着临床前数据、毒理学结果和未来计划将纳入简报 将在C类会议申请中提交给FDA的文件包。

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.