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  • Title: 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.
    Author: Weimer ET, Ervin SE, Wozniak DJ, Mizel SB.
    Journal: Vaccine; 2009 Nov 12; 27(48):6762-9. PubMed ID: 19744586.
    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.
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