Co-encapsulation of IroN and IL-12 as an Extra-intestinal E. coli Vaccine.

描述(由申请人提供)：尽管最近在治疗和预防传染病方面取得了进展，但对世界卫生的威胁仍在继续增加。禽流感等新的人畜共患病病毒株的传播，以及大肠杆菌等长期存在的病原体对抗生素的抗药性形式的出现，突显了不断进化的病原体的危险。在这个传染病威胁不断扩大的时代，新型、有效和实用的疫苗佐剂的开发已经相当滞后。根据其作用机制，佐剂可分为1)递送系统或2)免疫增强剂。免疫增强剂，如细胞因子，直接激活免疫系统。递送系统佐剂用于浓缩或靶向APC的疫苗抗原，或共同定位抗原和免疫增强剂。TreatyX公司使用专利的相转化纳米胶囊(PIN)技术来创造生物佐剂，该佐剂结合了免疫增强剂和递送系统的特性。为此，TreatyX公司开发了一种基于微粒的缓释细胞因子佐剂配方，可以诱导高效的TH1型T细胞和抗体反应。大量的肿瘤疫苗研究已经证明了该配方有效性的原则证据。最近，TreatyX公司开发了第二代纳米颗粒配方(TPX-506)，该配方在室温下可生物稳定至少一年，使其成为世界不发达地区预防传染病疫苗的理想佐剂。本应用将在小鼠尿路感染模型中测试TPX-506对肠外致病性大肠杆菌(ExPEC)的疗效。由大肠杆菌引起的肠外感染的多样性、频率、潜在严重性和经济影响与任何细菌感染一样大。由于目前没有其他疫苗可用，这种疫苗的成功生产将解决细菌预防市场的一个重大缺口。 公共卫生相关性-项目叙述：由大肠杆菌引起的肠道外感染的多样性、频率、潜在严重性和经济影响与任何细菌感染一样大。这项应用将测试TPX-506疫苗对肠外致病性大肠杆菌(ExPEC)感染的效果。由于目前没有其他疫苗可用，这种疫苗的成功生产将解决细菌预防市场的一个重大缺口。

DESCRIPTION (provided by applicant): Despite recent advances in the treatment and prevention of infectious disease, the threat to world health continues to grow. The spread of new zoonotic viral strains like avian influenza and the emergence of antibiotic resistant forms of long established pathogens such E. coli underscores the danger from ever evolving pathogens. In this era of expanding infectious threats, the development of novel, effective and practical vaccine adjuvants has lagged considerably. Adjuvants can be classified as 1) delivery systems or 2) immune potentiators on the basis of their mechanism of action. Immune potentiators, such as cytokines, activate the immune system directly. Delivery system adjuvants serve to concentrate or target vaccine antigens to APCs or to co-localize antigens and immune potentiators. TherapyX, Inc. uses the proprietary phase inversion nanoencapsulation (PIN) technology to create biological adjuvants that combine the properties of an immune potentiator and a delivery system. To this end, TherapyX, Inc. has developed a particulate-based, sustained-release cytokine adjuvant formulation that can induce highly effective TH1 type T-cell and antibody responses. Proof of principle for the efficacy of this formulation has been demonstrated in numerous tumor vaccine studies. More recently, TherapyX, Inc. developed a second generation nanoparticle formulation (TPX-506) that is biologically stable at room temperature for at least one year; making this an ideal adjuvant for vaccination against infectious disease in underdeveloped areas of the world. This application will test the efficacy of TPX-506 against extraintestinal pathogenic Escherichia coli (ExPEC) in a mouse urinary tract infection model. The diversity, frequency, potential severity, and economic impact of extraintestinal infections due to E. coli are as great as for any bacterial infection. With no other current vaccines available, the successful production this vaccine will address a significant gap in the bacterial prophylaxis market. PUBLIC HEALTH RELEVANCE - PROJECT NARRATIVE: The diversity, frequency, potential severity, and economic impact of extraintestinal infections due to E. coli are as great as for any bacterial infection. This application will test the efficacy of the TPX-506 vaccine against extraintestinal pathogenic Escherichia coli (ExPEC) infection. With no other current vaccines available, the successful production this vaccine will address a significant gap in the bacterial prophylaxis market.