title: Francisella tularensis type B ΔdsbA mutant protects against type A strain and induces strong inflammatory cytokine and Th1-like antibody response in vivo.
abstract: Francisella tularensis subspecies tularensis is a highly virulent intracellular bacterial pathogen, causing the disease tularemia. However, a safe and effective vaccine for routine application against F. tularensis has not yet been developed. We have recently constructed the deletion mutants for the DsbA homolog protein (ΔdsbA/FSC200) and a hypothetical protein IglH (ΔiglH/FSC200) in the type B F. tularensis subsp. holarctica FSC200 strain, which exerted different protection capacity against parental virulent strain. In this study, we further investigated the immunological correlates for these different levels of protection provided by ΔdsbA/FSC200 and ΔiglH/FSC200 mutants. Our results show that ΔdsbA/FSC200 mutant, but not ΔiglH/FSC200 mutant, induces an early innate inflammatory response leading to strong Th1-like antibody response. Furthermore, vaccination with ΔdsbA/FSC200 mutant, but not with ΔiglH/FSC200, elicited protection against the subsequent challenge with type A SCHU S4 strain in mice. An immunoproteomic approach was used to map a spectrum of antigens targeted by Th1-like specific antibodies, and more than 80 bacterial antigens, including novel ones, were identified. Comparison of tularemic antigens recognized by the ΔdsbA/FSC200 post-vaccination and the SCHU S4 post-challenge sera then revealed the existence of 22 novel SCHU S4 specific antibody clones.
authors.affiliation: Department of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Trebesska 1575, Hradec Kralove 500 01, Czech Republic straskova@alga.cz.
authors.forename: Adela
authors.initials: A
authors.lastname: Straskova
authors.affiliation: Department of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Trebesska 1575, Hradec Kralove 500 01, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Spidlova
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Mou
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702-5011, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Worsham
authors.affiliation: Department of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Trebesska 1575, Hradec Kralove 500 01, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Putzova
authors.affiliation: Department of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Trebesska 1575, Hradec Kralove 500 01, Czech Republic.
authors.forename: Ivona
authors.initials: I
authors.lastname: Pavkova
authors.affiliation: Department of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Trebesska 1575, Hradec Kralove 500 01, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Stulik
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000145:classification / Q000201:enzymology / Q000276:immunology*; D008807:Mice, Inbred BALB C; D019704:Protein Disulfide-Isomerases / Q000172:deficiency*; D018417:Th1 Cells / Q000276:immunology*; D014406:Tularemia / Q000276:immunology / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D037521:Virulence Factors / Q000172:deficiency
chemical_list: D001428:Bacterial Vaccines; D016207:Cytokines; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D019704:Protein Disulfide-Isomerases
keywords: antibody response; cytokines; immunoproteomics; protection; tularemia