title: Genetic engineering of Francisella tularensis LVS for use as a novel live vaccine platform against Pseudomonas aeruginosa infections.
abstract: Francisella tularensis LVS (Live Vaccine Strain) is an attenuated bacterium that has been used as a live vaccine. Patients immunized with this organism show a very long-term memory response (over 30 years post vaccination) evidenced by the presence of indicators of robust cell-mediated immunity. Because F. tularensis LVS is such a potent vaccine, we hypothesized that this organism would be an effective vaccine platform. First, we sought to determine if we could genetically modify this strain to produce protective antigens of a heterologous pathogen. Currently, there is not a licensed vaccine against the important opportunistic bacterial pathogen, Pseudomonas aeruginosa. Because many P. aeruginosa strains are also drug resistant, the need for effective vaccines is magnified. Here, F. tularensis LVS was genetically modified to express surface proteins PilAPa, OprFPa, and FliCPa of P. aeruginosa. Immunization of mice with LVS expressing the recombinant FliCPa led to a significant production of antibodies specific for P. aeruginosa. However, mice that had been immunized with LVS expressing PilAPa or OprFPa did not produce high levels of antibodies specific for P. aerugionsa. Therefore, the recombinant LVS strain engineered to produce FliCPa may be able to provide immune protection against a P. aeruginosa challenge. However for future use of this vaccine platform, selection of the appropriate recombinant antigen is critical as not all recombinant antigens expressed in this strain were immunogenic.
authors.affiliation: a Biomedical Sciences Department ; West Virginia School of Osteopathic Medicine ; Lewisburg , WV USA.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Robinson
authors.forename: Brianna N
authors.initials: BN
authors.lastname: Kobe
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Schmitt
authors.forename: Brian
authors.initials: B
authors.lastname: Phair
authors.forename: Tricia
authors.initials: T
authors.lastname: Gilson
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Jung
authors.forename: Lawton
authors.initials: L
authors.lastname: Roberts
authors.forename: Jialin
authors.initials: J
authors.lastname: Liao
authors.forename: Chelsea
authors.initials: C
authors.lastname: Camerlengo
authors.forename: Brandon
authors.initials: B
authors.lastname: Chang
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Davis
authors.forename: Leah
authors.initials: L
authors.lastname: Figurski
authors.forename: Devin
authors.initials: D
authors.lastname: Sindeldecker
authors.forename: Joseph
authors.initials: J
authors.lastname: Horzempa
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology; D005604:Francisella tularensis / Q000276:immunology*; D005818:Genetic Engineering / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000276:immunology* / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity*; D014613:Vaccines, Attenuated / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; C553424:PilA protein, Francisella tularensis; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D036781:Fimbriae Proteins
keywords: FliC; Francisella; OprF; PilA; Pseudomonas; flagellum; pilus; recombinant DNA; vaccine