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

IroN 和 IL-12 共封装作为肠外大肠杆菌疫苗。

• 批准号: 7394780
• 负责人: Thomas F Conway
• 金额: $ 29.25万
• 依托单位: THERAPYX, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394780
• 关键词: Address; Adjuvant; Animals; Antibiotic Resistance; Antibodies; Antibody Formation; Antigens; Area; Avian Influenza; Bacterial Infections; Biological; Bladder; CD4 Positive T Lymphocytes; Cancer Vaccines; Cellular Immunity; Cessation of life; Communicable Diseases; Complement; Development; Dose; Drug Formulations; Economics; Encapsulated; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Frequencies; Generations; Goals; Growth; Healthcare; Immune; Immune Sera; Immune response; Immune system; Immunity; Immunization; In Vitro; Infection; Infection prevention; Infectious Agent; Interferons; Interleukin-12; Intestines; Iron; Kidney; Life; Localized; MF59; Marketing; Measures; Mediating; Medical Economics; Modeling; Mus; Organism; Particulate; Patients; Phase; Phase I Clinical Trials; Prevention; Property; Prophylactic treatment; Public Health; Published Comment; QS21; Refrigeration; Route; Saliva; Salts; Sepsis; Serum; Severities; Staining method; Stains; Standards of Weights and Measures; System; T-Lymphocyte; Technology; Temperature; Testing; Toxicity Tests; Urinary tract infection; Urine; Vaccinated; Vaccination; Vaccine Adjuvant; Vaccine Antigen; Vaccine Production; Vaccines; Viral; Work; World Health; aluminum sulfate; antimicrobial; bactericide; base; cytokine; design; nanoparticle; neutrophil; new technology; novel; pathogen; pathogenic Escherichia coli; response

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.

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，但对世界健康的威胁仍在继续增长。新的人畜共患病病毒株如禽流感的传播和长期存在的病原体如大肠杆菌的抗生素耐药形式的出现。大肠杆菌强调了不断进化的病原体的危险。在这个传染性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。佐剂可根据其作用机制分为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。递送系统佐剂用于将疫苗抗原浓缩或靶向APC或共定位抗原和免疫增强剂。TherapyX，Inc.使用专有的相转化纳米封装（PIN）技术来创建联合收割机了免疫增强剂和输送系统特性的生物佐剂。为此，TherapyX，Inc.已经开发了一种基于颗粒的持续释放细胞因子佐剂制剂，其可以诱导高效的TH 1型T细胞和抗体应答。在许多肿瘤疫苗研究中已经证明了该制剂有效性的原理证明。最近，TherapyX，Inc.开发了第二代纳米颗粒制剂（TPX-506），在室温下生物稳定至少一年;使其成为世界欠发达地区预防传染病疫苗接种的理想佐剂。本申请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）的有效性。大肠杆菌肠外感染的多样性、频率、潜在严重程度和经济影响。大肠杆菌的感染率和任何细菌感染一样高。由于目前没有其他可用的疫苗，这种疫苗的成功生产将解决细菌预防市场的重大空白。 公共卫生相关性-项目叙述：由于大肠埃希氏菌引起的肠外感染的多样性，频率，潜在的严重性和经济影响。大肠杆菌的感染率和任何细菌感染一样高。本申请将检测TPX-506疫苗对肠外致病性大肠杆菌（ExPEC）感染的有效性。由于目前没有其他可用的疫苗，这种疫苗的成功生产将解决细菌预防市场的重大空白。