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Infection and Immunity, June 2004, p. 3336-3343, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3336-3343.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Recombinant Mycobacterium bovis BCG Expressing the Sm14 Antigen of Schistosoma mansoni Protects Mice from Cercarial Challenge

Paula B. Varaldo,1 Luciana C. C. Leite,1* Waldely O. Dias,1 Eliane N. Miyaji,1 Fabio I. G. Torres,1 Vera C. Gebara,1 Geraldo R. G. Armôa,2 Adriano S. Campos,2 Denise C. S. Matos,2 Nathalie Winter,3 Brigitte Gicquel,3,4 Mônica M. Vilar,5 Johnjoe McFadden,6 Marilia S. Almeida,7 Miriam Tendler,5* and Douglas McIntosh2,{dagger}

Centro de Biotecnologia, Instituto Butantan, São Paulo,1 Laboratory of Recombinant Technology, Institute of Immunobiological Technology (Bio-Manguinhos),2 Department of Helminthology, Oswaldo Cruz Foundation, Rio de Janeiro,5 Microbiology and Parasitology Department, Federal University of Santa Catarina, Florianópolis, Brazil,7 Laboratoire du BCG,3 Unité de Génetique Mycobactérienne, Institut Pasteur, Paris, France,4 University of Surrey, Surrey, England6

Received 26 November 2003/ Returned for modification 14 January 2004/ Accepted 19 February 2004

The Sm14 antigen of Schistosoma mansoni was cloned and expressed in Mycobacterium bovis BCG as a fusion with the Mycobacterium fortuitum ß-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.


* Corresponding author. Mailing address for Luciana Leite: Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo SP, Brazil. Phone and fax: 55-11-3726-9150. E-mail: lccleite{at}butantan.gov.br. Mailing address for Miriam Tendler: Department of Helminthology, Instituto Oswaldo Cruz, Avenida Brasil 4365, CEP 21045-900 Rio de Janeiro, Brazil. Phone: 55-21-2598-4361. Fax: 55-21-2260-4866. E-mail: mtendler{at}ioc.fiocruz.br.

Editor: D. L. Burns

{dagger} Present address: Research and Productivity Council, Fredericton, Canada.


Infection and Immunity, June 2004, p. 3336-3343, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3336-3343.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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