Recombinant Mycobacterium bovis BCG expressing the Sm14 antigen of Schistosoma mansoni protects mice from cercarial challenge.
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.
Varaldo
Paula B
PB
Centro de Biotecnologia, Instituto Butantan, São Paulo SP, Brazil.
Leite
Luciana C C
LC
Dias
Waldely O
WO
Miyaji
Eliane N
EN
Torres
Fabio I G
FI
Gebara
Vera C
VC
Armôa
Geraldo R G
GR
Campos
Adriano S
AS
Matos
Denise C S
DC
Winter
Nathalie
N
Gicquel
Brigitte
B
Vilar
Mônica M
MM
McFadden
Johnjoe
J
Almeida
Marilia S
MS
Tendler
Miriam
M
McIntosh
Douglas
D
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
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