title: A Synthetic Tul4 and FopA Peptide Cocktail of Francisella tularensis Induces Humoral and Cell-Mediated Immune Responses in Mice.
abstract: Francisella tularensis is a highly virulent pathogen of humans and other mammals. Moreover, F. tularensis has been designated a category A biothreat agent, and there is growing interest in the development of a protective vaccine. In the present study, we determine the in vitro and in vivo immune responses of a subunit vaccine composed of recombinant peptides Tul4 and FopA from epitopes of the F. tularensis outer membrane proteins. The recombinant peptides with adjuvant CpG induced robust immunophenotypic change of dendritic cell (DC) maturation and secretion of inflammatory cytokines (IL-6, IL-12). In addition, the matured DCs enabled ex vivo proliferation of naive splenocytes in a mixed lymphocyte reaction. Lastly, we determined the in vivo immune response by assessment of antibody production in C57BL/ 6 mice. Total IgG levels were produced after immunization and peaked in 6 weeks, and moreover, Tul4-specific IgG was confirmed in the mice receiving peptides with or without CpG. Based on these results, we concluded that the recombinant peptides Tul4 and FopA have immunogenicity and could be a safe subunit vaccine candidate approach against F. tularensis.
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Hanseul
authors.initials: H
authors.lastname: Oh
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: C-Yoon
authors.initials: CY
authors.lastname: Kim
authors.affiliation: The 5th R&D Institute-3, Agency for Defense Development, Daejeon 34186, Republic of Korea.
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Kim
authors.affiliation: The 5th R&D Institute-3, Agency for Defense Development, Daejeon 34186, Republic of Korea.
authors.forename: Gyeung-Haeng
authors.initials: GH
authors.lastname: Hur
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D005604:Francisella tularensis / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000032:analysis; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D014406:Tularemia; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C083436:FopA protein, Francisella tularensis; D007378:Interleukins; D008074:Lipoproteins; D014614:Vaccines, Synthetic; C075214:TUL4 protein, Francisella tularensis
keywords: FopA; Francisella tularensis; Tul4; immune response; subunit vaccine