Affiliation:
1. Department of Microbiology and Immunology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157
2. Department of Pathology, Division of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157
Abstract
ABSTRACT
Although chronic
Pseudomonas aeruginosa
infection is the major cause of morbidity and mortality in cystic fibrosis (CF) patients, there is no approved vaccine for human use against
P. aeruginosa
. The goal of this study was to establish whether a multivalent vaccine containing
P. aeruginosa
type A and B flagellins as well as the outer membrane proteins OprF and OprI would promote enhanced clearance of
P. aeruginosa
. Intramuscular immunization with flagellins and OprI (separate) or OprI-flagellin fusion proteins generated significant antiflagellin immunoglobulin G (IgG) responses. However, only the fusions of OprI with type A and type B flagellins generated OprI-specific IgG. Immunization with a combination of OprF epitope 8 (OprF
311-341
), OprI, and flagellins elicited high-affinity IgG antibodies specific to flagellins, OprI, and OprF that individually promoted extensive deposition of C3 on
P. aeruginosa
. Although these antibodies exhibited potent antibody-dependent complement-mediated killing of nonmucoid bacteria, they were significantly less effective with mucoid isolates. Mice immunized with the OprF
311-341
-OprI-flagellin fusion had a significantly lower bacterial burden three days postchallenge and cleared the infection significantly faster than control mice. In addition, mice immunized with the OprF
311-341
-OprI-flagellin fusion had significantly less inflammation and lung damage throughout the infection than OprF-OprI-immunized mice. Based on our results, OprF
311-341
-OprI-flagellin fusion proteins have substantial potential as components of a vaccine against nonmucoid
P. aeruginosa
, which appears to be the phenotype of the bacterium that initially colonizes CF patients.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference71 articles.
1. Bates, J. T., A. N. Honko, A. H. Graff, N. D. Kock, and S. B. Mizel. 2008. Mucosal adjuvant activity of flagellin in aged mice. Mech. Ageing Dev.129:271-281.
2. J. Immunol.
3. Benner, R., A. van Oudenaren, and G. Koch. 1981. Induction of antibody formation in mouse bone marrow, p. 247-262. In I. Lefkovits and B. Pernis (ed.), Immunological methods, vol. II. Academic Press, Inc., New York, NY.
4. Intranasal Administration of Synthetic Recombinant Peptide-Based Vaccine Protects Mice from Infection by
Schistosoma mansoni
5. Brazova, J., A. Sediva, D. Pospisilova, V. Vavrova, P. Pohunek, J. Macek, J. Bartunkova, and H. Lauschmann. 2005. Differential cytokine profile in children with cystic fibrosis. Clin. Immunol.115:210-215.
Cited by
68 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献