title: Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding protein in live attenuated Salmonella vaccine strains.
abstract: Fatty acid-binding proteins (FABPs) are candidate molecules for vaccines against several parasitic platyhelminths. A FABP from the cestode Echinococcus granulosus (EgDf1) was expressed in Salmonella vaccine strains as a C-terminal fusion to fragment C of tetanus toxin (TetC) by using expression vector pTECH. The fusion protein was equally expressed in several attenuated vaccine strains derived from bacteria with different genetic backgrounds and different attenuating mutations. Single-dose immunization experiments with the aroA Salmonella typhimurium strain SL3261 carrying the pTECH-EgDf1 construct were conducted with mice, using both the intravenous and the oral routes. Surprisingly, the antibody response to EgDf1 and the antigen-specific cytokine production in spleen cells were stronger in mice immunized orally. Furthermore, immune mouse sera strongly reacted with fixed sections of the worm's larval stage. Analysis of the isotype distribution of the specific anti-EgDf1 antibodies showed similar production of immunoglobulin G1 (IgG1) and IgG2a together with specific IgA antibodies. In addition, stimulation of spleen cells from mice immunized with the different constructs with either Salmonella lysate, TetC, or EgDf1 showed that, together with Th1-related cytokines (gamma interferon and interleukin 2 [IL-2]), significant levels of a Th2 cytokine (IL-5) were produced specifically, indicating a Th2 component to the response to the Salmonella carrier and to the recombinant antigens. Salmonellae expressing the TetC-rEgDfl fusion are currently under evaluation as potential vaccines against E. granulosus.
authors.affiliation: Department of Microbiology, The Medical School, University of Newcastle, Newcastle Upon Tyne, United Kingdom. crtn@bilbo.edu.uy
authors.forename: J A
authors.initials: JA
authors.lastname: Chabalgoity
authors.forename: J A
authors.initials: JA
authors.lastname: Harrison
authors.forename: A
authors.initials: A
authors.lastname: Esteves
authors.forename: R
authors.initials: R
authors.lastname: Demarco de Hormaeche
authors.forename: R
authors.initials: R
authors.lastname: Ehrlich
authors.forename: C M
authors.initials: CM
authors.lastname: Khan
authors.forename: C E
authors.initials: CE
authors.lastname: Hormaeche
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology*; D003001:Cloning, Molecular; D004446:Echinococcus / Q000276:immunology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018996:Myelin P2 Protein / Q000276:immunology*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012475:Salmonella / Q000235:genetics*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007376:Interleukin-2; D015848:Interleukin-5; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D015847:Interleukin-4; D007371:Interferon-gamma