Kamei et al, Multi-factorial acquired immunity against P. aeruginosa, Page 1 1 Revised Manuscript IAI01139-10 Version 2 Mucosal Vaccination with a Multivalent, Live-attenuated Vaccine Induces Multi-factorial Immunity Against Pseudomonas aeruginosa Acute L

Kamei et al, Multi-factorial acquired immunity against P. aeruginosa, Page 2 2 Abstract 1 Many animal studies investigating adaptive immune effectors important for protection against 2 Pseudomonas aeruginosa have implicated opsonic antibody to the antigenically-variable 3 lipopolysaccharide (LPS) O-antigens as a primary effector. However, active and passive 4 vaccination of humans against these antigens has not shown clinical efficacy. We hypothesized 5 that optimal immunity would require inducing multiple immune effectors targeting multiple 6 bacterial antigens. Therefore we evaluated a multivalent, live-attenuated mucosal vaccination 7 strategy in a murine model of acute P. aeruginosa pneumonia to assess the contributions towards 8 protective efficacy of various bacterial antigens and host immune effectors. Vaccines combining 9 3 or 4 attenuated strains having different LPS serogroups were associated with the highest 1