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.

Public Health Relevance

A vaccine against lung infections with Pseudomonas aeruginosa is needed, especially for individuals with cystic fibrosis. This proposal aims to evaluate a novel vaccine that will be administered to the respiratory tract, assess its safety in various animal models and so provide the basis for a human trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
4R01AI103341-04
Application #
9040866
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Lu, Kristina
Project Start
2013-05-16
Project End
2017-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Gomi, Rika; Sharma, Anurag; Wu, Wenzhu et al. (2017) Post-exposure immunization by capsid-modified AdC7 vector expressing Pseudomonas aeruginosa OprF clears P. aeruginosa respiratory infection. Vaccine 35:7174-7180
Quigley, Kathryn J; Reynolds, Catherine J; Goudet, Amelie et al. (2015) Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F. Am J Respir Crit Care Med 191:1250-64