Bivalent flagellin immunotherapy protects mice against Pseudomonas aeruginosa infections in both acute pneumonia and burn wound models

Pseudomonas aeruginosa infections are a serious challenge to therapy because of the complex pathogenesis and paucity of new effective antibiotics, thus renewing interest in antibody-based therapeutic strategies. Immunotherapy strategies typically target selected virulence factors that are expressed by the majority of clinical strains of P. aeruginosa, particularly because virulence factors mediate infection. Type a and b flagellins (flagellin a+b) of P. aeruginosa are acute virulence factors that play a major role in the establishment of infection. Here we evaluate the protective efficacy of antibodies raised against flagellin a+b in both acute pneumonia and burn models. A combination strategy using antibodies against flagellin a+b provided greater protection against cell invasion and enhanced opsono-phagocytosis and decreased motility of P. aeruginosa strains, compared to strategies using antibodies against a single flagellin. Antibodies against flagellin a+b-protected mice infected with P. aeruginosa strains significantly reduced bacterial dissemination from the site of infection to the liver and spleen. Passive immunization with antibodies against flagellin a+b led to an efficacious protection against P. aeruginosa infection in both acute pneumonia and burn models. (C) 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.