title: Epitope-based vaccination against pneumonic tularemia.
abstract: Francisella tularensis, the etiological agent of tularemia, is one of the most infectious bacterial pathogens known. No vaccine is currently approved for public use. Previously, we identified epitopes recognized specifically by T cells obtained from individuals following infection with F. tularensis. Here, we report that a subunit vaccine constructed based upon these epitopes elicited protective immunity in "humanized" HLA class II (DRB1*0401) transgenic mice. Vaccinated mice challenged intratracheally with a lethal dose of F. tularensis (Live Vaccine Strain) exhibited a rapid increase in pro-inflammatory cytokine production and diminished number of organisms in the lungs, and a concurrent increased rate of survival. These results demonstrate the efficacy of an epitope-based tularemia vaccine and suggest that such an approach might be widely applicable to the development of vaccines specific for intracellular bacterial pathogens.
authors.affiliation: Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI, United States. sgregory@lifespan.org
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
authors.forename: Stephanie
authors.initials: S
authors.lastname: Mott
authors.forename: Jennifer
authors.initials: J
authors.lastname: Phung
authors.forename: Jinhee
authors.initials: J
authors.lastname: Lee
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.forename: Julie A
authors.initials: JA
authors.lastname: McMurry
authors.forename: William
authors.initials: W
authors.lastname: Martin
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005604:Francisella tularensis / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D014406:Tularemia / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000276:immunology; D022223:Vaccines, Subunit
chemical_list: D001428:Bacterial Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D022223:Vaccines, Subunit