Experimental Gonococcal Vaccine

实验性淋球菌疫苗

• 批准号: 9337065
• 负责人: Yingru Liu
• 金额: $ 80.52万
• 依托单位: THERAPYX, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337065
• 关键词: Animal Model; Antibiotics; Antibodies; Antibody Response; Antibody Specificity; Antibody titer measurement; Antigens; Applications Grants; Biological Availability; Centers for Disease Control and Prevention (U.S.); Clinical; Clinical Research; Communicable Diseases; Data; Detergents; Development; Disease; Drug Kinetics; Embryonic and Fetal Development; Formulation; Frequencies; Future; Generations; Genital system; Gonorrhea; Human; Immune response; Immune system; Immunity; Immunization; Immunosuppression; Incidence; Infection; Interferons; Interleukin-12; Intranasal Administration; Intravaginal Administration; Measures; Membrane; Multi-Drug Resistance; Mus; Neisseria gonorrhoeae; Particulate; Phase; Preparation; Preventive vaccine; Progress Reports; Prophylactic treatment; Public Health; Rattus; Regimen; Reporting; Research Design; Resistance; Rodent; Route; Serum; Shapes; Small Business Innovation Research Grant; T-Lymphocyte; Testing; Th1 Cells; Toxic effect; Toxicology; Vaccination; Vaccines; Vesicle; adaptive immune response; combinatorial; cytokine; male; meetings; mouse model; nanoparticulate; nonhuman primate; novel strategies; pre-clinical; prophylactic; prototype; public health relevance; reproductive; reproductive toxicity; reproductive tract; resistant strain; response; vaccine delivery

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.

抽象的 淋病奈瑟菌（淋病）的生殖道感染不会引起特异性保护状态 尽管采取了公共卫生措施，但这种疾病仍然持续存在。 频率之高令人难以接受；没有针对它的疫苗，甚至对最新一代的疫苗也有耐药性 最近的研究结果表明，淋病奈瑟菌会破坏免疫系统。 系统为了自身的利益，通过引发它可以生存的先天反应，并通过抑制特定的适应性 然而，这种诱导的免疫抑制可以通过治疗来逆转。 已经建立了有效重定向针对淋病奈瑟菌的免疫反应的方法。 使用公认的小鼠模型来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，目前的疫苗原型是 GvaX12®（一种组合疫苗）。 我们专有的缓释纳米颗粒白细胞介素 12 和淋球菌外衣的配方 膜囊泡）诱导抗淋球菌 T 细胞和抗体反应，并产生针对 同源和异源菌株长达 6 个月。在此 II 期应用中，我们将定义、优化、 并验证疫苗接种方案，包括鼻内给药途径。 针对天然存在的淋病奈瑟菌不同菌株的交叉保护奠定了基础，并开始初步研究 药代动力学和毒理学研究，为随后的非人类毒理学测试做准备 灵长类动物的毒理学结果和未来计划将与临床前数据一起纳入简报中。 该包将在 C 类会议请求中提交给 FDA。