title: Recombinant Mycobacterium bovis BCG expressing the Sm14 antigen of Schistosoma mansoni protects mice from cercarial challenge.
abstract: The Sm14 antigen of Schistosoma mansoni was cloned and expressed in Mycobacterium bovis BCG as a fusion with the Mycobacterium fortuitum beta-lactamase protein under the control of its promoter, pBlaF*; the protein was localized in the bacterial cell wall. The rBCG-Sm14 strain was shown to be relatively stable in cultured murine and bovine monocytes in terms of infectivity, bacterial persistence, and plasmid stability. The immunization of mice with rBCG-Sm14 showed no induction of anti-Sm14 antibodies; however, splenocytes of immunized mice released increased levels of gamma interferon upon stimulation with recombinant Sm14 (rSm14), indicating an induction of a Th1-predominant cellular response against Sm14. Mice immunized with one or two doses of rBCG-Sm14 and challenged with live S. mansoni cercaria showed a 48% reduction in worm burden, which was comparable to that obtained by immunization with three doses of rSm14 purified from Escherichia coli. The data presented here further enhance the status of Sm14 as a promising candidate antigen for the control of schistosomiasis and indicate that a one-dose regimen of rBCG-Sm14 could be considered a convenient means to overcome many of the practical problems associated with the successful implementation of a multiple-dose vaccine schedule in developing countries.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo SP, Brazil.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Varaldo
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
authors.forename: Waldely O
authors.initials: WO
authors.lastname: Dias
authors.forename: Eliane N
authors.initials: EN
authors.lastname: Miyaji
authors.forename: Fabio I G
authors.initials: FI
authors.lastname: Torres
authors.forename: Vera C
authors.initials: VC
authors.lastname: Gebara
authors.forename: Geraldo R G
authors.initials: GR
authors.lastname: Armôa
authors.forename: Adriano S
authors.initials: AS
authors.lastname: Campos
authors.forename: Denise C S
authors.initials: DC
authors.lastname: Matos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Mônica M
authors.initials: MM
authors.lastname: Vilar
authors.forename: Johnjoe
authors.initials: J
authors.lastname: McFadden
authors.forename: Marilia S
authors.initials: MS
authors.lastname: Almeida
authors.forename: Miriam
authors.initials: M
authors.lastname: Tendler
authors.forename: Douglas
authors.initials: D
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D050612:Fatty Acid Transport Proteins; D005260:Female; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes; D009163:Mycobacterium bovis / Q000235:genetics*; D019907:Mycobacterium fortuitum / Q000201:enzymology / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D012555:Schistosomiasis mansoni / Q000469:parasitology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
chemical_list: D000909:Antibodies, Helminth; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D015801:Helminth Proteins; D026901:Membrane Transport Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C068709:SM14 protein, Schistosoma mansoni; D007371:Interferon-gamma; D001618:beta-Lactamases