Therapy and Prophylaxis for Genital Tract Infection

生殖道感染的治疗和预防

基本信息

批准号：
8522874
负责人：
Yingru Liu
金额：
$ 30万
依托单位：
THERAPYX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2014-06-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8522874
关键词：
Animal Model Antibiotics Antibodies Antibody Formation Antigenic Variation Biodegradable microsphere CD4 Positive T Lymphocytes Centers for Disease Control and Prevention (U.S.)Clinical Trials Communicable Diseases Complex Disease Dose Drug Kinetics Encapsulated Evaluation Frequencies Future Generations Genital system Goals Gonorrhea Immune Immune response Immune system Immunity Incidence Infection Interleukin-12 Intervention Lead Measures Memory Multi-Drug Resistance Mus Neisseria gonorrhoeae Outcome Phase Phase I Clinical Trials Preparation Prophylactic treatment Public Health Reporting Resistance Schedule Serum Small Business Innovation Research Grant T-Lymphocyte Testing Th2 Cells Tissues Toxic effect United States Vaccines Vagina Vaginal Route of Drug Administration Work adaptive immunity base cytokine design dosage genital secretion lymph nodes mouse model novel novel strategies public health relevance resistant strain response secondary infection

项目摘要

DESCRIPTION (provided by applicant): Genital tract infection with Neisseria gonorrhoeae (gonorrhea) does not induce a state of specific protective immunity and 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. New findings reveal 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. This SBIR application seeks to develop a novel strategy utilizing a proprietary product already developed by TherapyX, Inc., for intravaginal application to redirect the immune response effectively against N. gonorrhoeae. The product will be evaluated in a mouse model of vaginal gonococcal infection that has become accepted as the only currently available animal model. Phase I aims to establish proof-of- principle that the product can induce anti-gonococcal T-cell and antibody responses against the existing infection and accelerate its clearance, and moreover can be recalled to elicit protection against re-infection. The duration of the recall effect, and its ability to afford protection againt different strains of N. gonorrhoeae, will be determined. Successful completion of Phase I will lead to Phase II in which product dosage will be optimized, toxicity will be tested, and cross-protection against a diversity of naturally occurring strains of N. gonorrhoeae and long-term efficacy will be evaluated in preparation for clinical trial.

描述（申请人提供）：淋病奈瑟菌（淋病）的生殖道感染不会诱发特异性保护性免疫状态，并且可以反复获得。尽管采取了公共卫生措施，该疾病的发病率仍高得令人无法接受；目前还没有针对这种疾病的疫苗，甚至对最新一代抗生素的耐药性仍在不断出现。新的研究结果表明，淋病奈瑟菌为了自身利益而破坏免疫系统，通过引发使其能够生存的先天反应，并通过抑制可消除它的特定适应性反应。该 SBIR 应用旨在利用 TherapyX, Inc. 已开发的专有产品开发一种新策略，用于阴道内应用，以有效重定向针对淋病奈瑟菌的免疫反应。该产品将在阴道淋球菌感染小鼠模型中进行评估，该模型已成为目前唯一可用的动物模型。第一阶段的目的是建立原理证明，证明该产品可以诱导抗淋球菌 T 细胞和抗体针对现有感染的反应并加速其清除，此外还可以被召回以引发针对再次感染的保护。将确定召回效应的持续时间及其针对不同淋病奈瑟菌菌株提供保护的能力。第一阶段的成功完成将进入第二阶段，其中将优化产品剂量，测试毒性，并评估针对多种天然存在的淋病奈瑟菌菌株的交叉保护和长期疗效，为临床做好准备审判。