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.
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.
authors.affiliation: Department of Microbiology & Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Weimer
authors.forename: Sean E
authors.initials: SE
authors.lastname: Ervin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wozniak
authors.forename: Steven B
authors.initials: SB
authors.lastname: Mizel
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000918:Antibody Specificity; D001426:Bacterial Proteins / Q000276:immunology; D002522:Chlorocebus aethiops / Q000276:immunology; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology; D005260:Female; D005408:Flagellin / Q000276:immunology*; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D008074:Lipoproteins / Q000276:immunology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control*; D054406:Pseudomonas Vaccines / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D003176:Complement C3; D007074:Immunoglobulin G; D008074:Lipoproteins; D054406:Pseudomonas Vaccines; D011993:Recombinant Fusion Proteins; C060507:outer membrane lipoprotein I, Bacteria; D005408:Flagellin; C416532:flaB flagellin