Lipid/DNA/Antigen Complexes for Pseudomonas vaccines

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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.