Post-exposure immunization by capsid-modified AdC7 vector expressing Pseudomonas aeruginosa OprF clears P. aeruginosa respiratory infection

• Published in: Vaccine Vol. 35; no. 51; pp. 7174 - 7180
• Main Authors: Gomi, Rika, Sharma, Anurag, Wu, Wenzhu, Sung, Biin, Worgall, Stefan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 18.12.2017; Elsevier Limited
• Subjects: Adenoviridae - genetics; Agar; Age; Animals; Antibodies, Bacterial - biosynthesis; Antibodies, Bacterial - blood; Antigens; Arginine; Aspartic acid; Bacteria; Bacterial Proteins - administration & dosage; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Beads; Capsid Proteins - genetics; Capsid Proteins - immunology; Capsid-modified non-human primate adenoviral vector; Chronic infection; Chronic obstructive pulmonary disease; Chronic pulmonary infections; Colonization; Cystic fibrosis; Cystic Fibrosis - microbiology; Dendritic cells; Expression vectors; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Genetic Vectors - immunology; Glycine; HIV; Human immunodeficiency virus; Immune clearance; Immune response (cell-mediated); Immune response (humoral); Immunity; Immunization; Immunization - methods; Immunoglobulin G - biosynthesis; Immunoglobulin G - blood; Infections; Laboratories; Lung - immunology; Lungs; Measles; Membrane proteins; Mice; Mineral oils; Mucosal immunity; Mucosal immunization; Pathogens; Patients; Porins; Post-exposure immunization; Post-Exposure Prophylaxis - methods; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Pseudomonas Infections - therapy; Rats; Rats, Sprague-Dawley; Respiratory tract; Respiratory tract infection; Respiratory Tract Infections - immunology; Respiratory Tract Infections - microbiology; Respiratory Tract Infections - therapy; Rodents; Serotypes; Trachea; Vaccines; Chronic pulmonary infections; Post-exposure immunization; Pseudomonas aeruginosa; Cystic fibrosis; Capsid-modified non-human primate adenoviral vector; Mucosal immunization
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.10.078

•A vaccine against established P. aeruginosa respiratory infections would be helpful.•Capsid-modified AdC7 vectors are potent inducers of respiratory mucosal immunity.•Immunization with AdC7OprF.RGD against established P. aeruginosa lung infections was evaluated.•AdC7OprF.RGD immunization induced robust humoral and cellular immunity against P. aeruginosa.•The induced immunity enhanced clearance of P. aeruginosa from rodent lungs. Respiratory infections with Pseudomonas aeruginosa are major health problems, particularly in patients with cystic fibrosis (CF). No vaccine against P. aeruginosa is yet available. A vaccine that controls colonization of the respiratory tract with P. aeruginosa could be useful to prevent chronic infection and exacerbations. Replication-deficient adenoviral (Ad) vectors based on non-human serotypes are attractive vaccine platforms as they can circumvent the problem of pre-existing anti-Ad immunity in humans. The primate-based AdC7 vector AdC7OprF.RGD that expresses the outer membrane protein F (OprF) of P. aeruginosa (AdC7OprF) and that displays an integrin-binding arginine–glycine–aspartic acid (RGD) sequence is a potent inducer of lung mucosal and protective immunity. Here, we investigated the efficacy of immunization with AdC7OprF.RGD to clear an already established P. aeruginosa respiratory infection in mice (wild-type and CF) and rats. Intratracheal administration of the clinical P. aeruginosa strain RP73 embedded in agar beads was used to establish persistent infection. Subsequent intranasal immunization with AdC7OprF.RGD induced robust P. aeruginosa-specific systemic and mucosal, humoral and cellular immune responses. Importantly, the AdC7OprF.RGD immunized mice effectively cleared P. aeruginosa from the lungs. Likewise, immunization with AdC7OprF.RGD of CF mice and Sprague Dawley rats with established P. aeruginosa respiratory infection showed enhanced anti-Pseudomonas immune responses and increased clearance of P. aeruginosa from the lungs. These data suggest that AdC7OprF.RGD can be effective as a post-exposure vaccine and may be useful in clinical settings in particular for patients with CF who frequently harbor the bacteria over prolonged periods.