Immunization of young African green monkeys with OprF epitope 8-OprI-type A- and B-flagellin fusion proteins promotes the production of protective antibodies against nonmucoid Pseudomonas aeruginosa

Abstract

There is currently no approved vaccine against Pseudomonas aeruginosa, the major cause of morbidity and mortality in cystic fibrosis (CF) patients and a major pathogen in ventilated and burn patients. In a previous study, we demonstrated the immunization of mice with OprF(311-341)-OprI-type A- and B-flagellin fusion proteins dramatically enhanced clearance of nonmucoid P. aeruginosa. The goal of the current study was to evaluate the ability of OprF(311-341)-OprI-flagellins to elicit the production of protective IgG in young (4-6 months old) African green monkeys. Intramuscular immunization of African green monkeys with 1, 3, 10, or 30mug of OprF(311-341)-OprI-flagellins generated robust antigen-specific IgG responses. In addition, immunization with OprF(311-341)-OprI-flagellins elicited high-affinity anti-flagellins, OprI, and OprF IgG that individually promoted extensive deposition of complement component C3 on P. aeruginosa and synergized to facilitate maximal C3 deposition. Passive immunization of mice with plasma from OprF(311-341)-OprI-flagellins immunized monkeys significantly reduced lung bacterial burden three days post-challenge compared to mice that received pre-immunization plasma. Based on our results, OprF(311-341)-OprI-A- and B-flagellin fusion proteins are highly effective in mice and nonhuman primates and thus merit additional development as a potential vaccine for use in humans.