Lipid/DNA/Antigen Complexes for Pseudomonas vaccines

描述（由申请人提供）：Juarez BioTherapeutics正在开发和表征一种基于阳离子脂质载体和非编码DNA （CLDC）络合的独特先天免疫佐剂和刺激剂。该产品通过多种途径有效，包括肠外注射、呼吸和口服。脂基复合物与抗原（LADC）的结合产生了强大的佐剂作用以及对靶抗原的强大CTL反应。本提案的总体目的是通过制定针对革兰氏阴性菌铜绿假单胞菌III型毒素传递系统的疫苗来测试CLDC的佐剂效果。铜绿假单胞菌是呼吸机相关性肺炎（VAP）、严重烧伤、化疗引起的免疫抑制、囊性纤维化或留置导尿管患者中一种重要的条件致病菌。在这些患者中，铜绿假单胞菌通过释放外毒素引起疾病，外毒素损害或破坏周围宿主组织，促进生物体的传播，并使巨噬细胞的吞噬机制瘫痪。由于患者的类型有风险，假单胞菌感染通常发生在医院环境中。脓毒症假单胞菌的死亡率为20-50%，肺炎假单胞菌的死亡率为30-40%。本提案的具体目标是优化体外先天性免疫和体内特异性免疫的CLDC，并使用该优化配方来评估P. aeruginosa气管内给药的保护能力。如果成功，第二阶段将比较cldc介导的PcrV疫苗接种与其他假单胞菌抗原，在假单胞菌感染的不同阶段进行预防性和治疗性疫苗接种。

DESCRIPTION (provided by applicant): Juarez BioTherapeutics is developing and characterizing a unique adjuvant and stimulant of innate immunity based on the complexation of a cationic lipid carrier and non-coding DNA (CLDC). The product is effective via multiple routes including parenteral, respiratory and oral. The combination of the lipid-based complex with antigen (LADC) results in a potent adjuvant effect as well as a robust CTL response to the target antigen. The overall purpose of this proposal is to test the adjuvant effect of CLDC by formulating a vaccine against the type III toxin delivery system of the gram negative bacteria Pseudomonas aeruginosa. P. aeruginosa is a significant opportunistic pathogen in patients with ventilator associated pneumonia (VAP), severe bums, immunosuppression due to chemotherapy, cystic fibrosis, or patients with indwelling catheters. In these patients, P. aeruginosa causes disease by the release of exotoxins, which damage or destroy the surrounding host tissue, promote dissemination of the organism and paralyze the phagocytic mechanism of macrophages. Because of the types of patients at risk, Pseudomonas infections usually occur in a hospital setting. Pseudomonas sepsis has a mortality rate of 20-50% and Pseudomonas pneumonia has a 30-40% mortality rate. The specific goals of this proposal are to optimize the CLDC for innate immunity in vitro, specific immunity in vivo, and use this optimal formulation to evaluate the ability to confer protection versus intratracheal administration of P. aeruginosa. If successful, Phase II will compare CLDC-mediated vaccination against PcrV with other Pseudomonas antigens for both prophylactic and therapeutic vaccine administration in various stages of established Pseudomonas infection.