title: Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF.
abstract: Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p>0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p>0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p<0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Krause
authors.forename: Wen Zhu
authors.initials: WZ
authors.lastname: Whu
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Xu
authors.forename: Ju
authors.initials: J
authors.lastname: Joh
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: Stefan
authors.initials: S
authors.lastname: Worgall
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018272:Porins / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C109237:OmpF protein; D018272:Porins; D007371:Interferon-gamma