title: Immunogenicity and protective efficacy of DNA vaccines encoding MAP0586c and MAP4308c of Mycobacterium avium subsp. paratuberculosis secretome.
abstract: Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of chronic enteritis of the small intestine in domestic and wild ruminants, causes substantial losses to livestock industry. Control of this disease is seriously hampered by the lack of adequate diagnostic tools, vaccines and therapies. In this study, we have evaluated the vaccine potential of two MAP proteins, i.e. MAP0586c and MAP4308c, previously identified by postgenomic and immunoproteomic analysis of MAP secretome as novel serodiagnostic antigens. Immunizations of BALB/c and C57BL/6 mice with plasmid DNA encoding MAP0586c and MAP4308c induced strong Th1 type immune responses to both antigens, whereas antibody responses were only induced upon immunization with DNA encoding MAP4308c. Homologous boosting of DNA vaccinated mice with recombinant protein resulted in strong antibody responses against both proteins. Using synthetic overlapping peptides, immunodominant H-2(d) and H-2(b) restricted Th1 T cell epitopes were identified. Finally, MAP infected mice generated strong MAP0586c-specific T cell responses and MAP0586c DNA vaccination could protect BALB/c but not C57BL/6 mice against MAP challenge mice to the same extent as the Mycobacterium bovis BCG vaccine, indicating that this putative transglycosylase is an interesting vaccine candidate that warrants further investigation.
authors.affiliation: Laboratory of Mycobacterial Immunology, Department Pasteur Institute, Scientific Institute of Public Health IPH-WIV-ISP, 642 Engelandstraat, B1180 Brussels, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Roupie
authors.forename: Baptiste
authors.initials: B
authors.lastname: Leroy
authors.forename: Valérie
authors.initials: V
authors.lastname: Rosseels
authors.forename: Virginie
authors.initials: V
authors.lastname: Piersoel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Noël-Georis
authors.forename: Marta
authors.initials: M
authors.lastname: Romano
authors.forename: Marc
authors.initials: M
authors.lastname: Govaerts
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Letesson
authors.forename: Ruddy
authors.initials: R
authors.lastname: Wattiez
authors.forename: Kris
authors.initials: K
authors.lastname: Huygen
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016927:Mycobacterium avium subsp. paratuberculosis / Q000235:genetics / Q000276:immunology*; D010283:Paratuberculosis / Q000517:prevention & control; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D019444:Vaccines, DNA