Mucosal Immunization Against P. aeruginosa by Modified Adenovirus Vectors

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DESCRIPTION (provided by applicant): Lung infections with Pseudomonas aeruginosa are a significant health problem for patients with bronchiectasis and cystic fibrosis. A vaccine against P. aeruginosa would be useful to prevent colonization and infection. Adenovirus vectors are efficient vaccine platforms for genetic vaccines and we have developed various Ad-based vaccines expressing the P. aeruginosa OprF protein. Our prior studies established that, the chimpanzee-based Ad vector (AdC7) expressing OprF and a peptide motif (RGD) that enhances infection of immune cells administered directly to the lung provides long term immunity and protection against P. aeruginosa. This project aims to evaluate AdC7RGD.OprF following administration to the lung in another rodent model and then develop a GLP-clinical AdC7RGD.OprF vector, including toxicology and efficacy evaluation in non-human primates. This would then lead to the clinical development of an AdC7-based vaccine for a clinical study.