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独特的先天免疫佐剂和刺激剂，该佐剂和刺激剂基于阳离子脂质载体和非编码DNA（CLDC）的复合。该产品通过多种途径有效，包括胃肠外、呼吸道和口服。基于脂质的复合物与抗原（LADC）的组合导致有效的佐剂作用以及对靶抗原的稳健的CTL应答。本提案的总体目的是通过配制针对革兰氏阴性菌铜绿假单胞菌的III型毒素递送系统的疫苗来测试CLDC的佐剂作用。 铜绿假单胞菌是呼吸机相关性肺炎（VAP）、严重烧伤、化疗所致免疫抑制、囊性纤维化或留置导管患者中的重要机会致病菌。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麻痹巨噬细胞的吞噬机制。由于处于危险中的患者类型，假单胞菌感染通常发生在医院环境中。假单胞菌败血症的死亡率为20-50%，假单胞菌肺炎的死亡率为30-40%。该提案的具体目标是优化CLDC的体外先天免疫性、体内特异性免疫性，并使用该最佳制剂来评价相对于铜绿假单胞菌的肠内给药提供保护的能力。如果成功，II期将比较CLDC介导的针对PcrV的疫苗接种与其他假单胞菌抗原在已建立的假单胞菌感染的各个阶段的预防性和治疗性疫苗施用。

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.