Recombinant Mycobacterium bovis BCG expressing the Sm14 antigen of Schistosoma mansoni protects mice from cercarial challenge

Infect Immun. 2004 Jun;72(6):3336-43. doi: 10.1128/IAI.72.6.3336-3343.2004.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Helminth / blood
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism
  • Cattle
  • Cells, Cultured
  • Fatty Acid Transport Proteins
  • Female
  • Helminth Proteins / genetics
  • Helminth Proteins / immunology*
  • Helminth Proteins / metabolism
  • Interferon-gamma / biosynthesis
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred BALB C
  • Monocytes
  • Mycobacterium bovis / genetics*
  • Mycobacterium fortuitum / enzymology
  • Mycobacterium fortuitum / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Schistosoma mansoni / growth & development
  • Schistosoma mansoni / immunology*
  • Schistosoma mansoni / pathogenicity
  • Schistosomiasis mansoni / parasitology
  • Schistosomiasis mansoni / prevention & control*
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Antibodies, Helminth
  • Carrier Proteins
  • Fatty Acid Transport Proteins
  • Helminth Proteins
  • Membrane Transport Proteins
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • SM14 protein, Schistosoma mansoni
  • Interferon-gamma
  • beta-Lactamases