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Infection and Immunity, October 2004, p. 6112-6124, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6112-6124.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Nucleic Acid Vaccination with Schistosoma mansoni Antioxidant Enzyme Cytosolic Superoxide Dismutase and the Structural Protein Filamin Confers Protection against the Adult Worm Stage

Rosemary M. Cook,1 Claudia Carvalho-Queiroz,1 Gregory Wilding,2 and Philip T. LoVerde1*

Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences,1 Department of Biostatistics, State University of New York, Buffalo, New York2

Received 21 May 2004/ Returned for modification 28 June 2004/ Accepted 7 July 2004

Schistosomiasis remains a worldwide endemic cause of chronic and debilitating illness. There are two paradigms that exist in schistosome immunology. The first is that the schistosomule stages are the most susceptible to immune killing, and the second is that the adult stage, through evolution of defense mechanisms, can survive in the hostile host environment. One mechanism that seems to aid the adult worm in evading immune killing is the expression of antioxidant enzymes to neutralize the effects of reactive oxygen and nitrogen species. Here, we challenge one paradigm by targeting adult Schistosoma mansoni worms for immune elimination in an experimental mouse model using two S. mansoni antioxidants, cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), and a partial coding sequence for a structural protein, filamin, as DNA vaccine candidates. DNA vaccination with SmCT-SOD induced a mean of 39% protection, filamin induced a mean of 50% protection, and SmGPX induced no protection compared to controls following challenge with adult worms by surgical transfer. B- and T-cell responses were analyzed in an attempt to define the protective immune mechanism(s) involved in adult worm killing. SmCT-SOD-immunized mice presented with a T1 response, and filamin-immunized mice showed a mixed T1-T2 response. We provide evidence for natural boosting after vaccination. Our results demonstrate that adult worms can be targeted for immune elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, 138 Farber Hall, School of Medicine and Biomedical Sciences, SUNY, Buffalo, NY 14214. Phone: (716) 829-2459. Fax: (716) 829-2169. E-mail: loverde{at}buffalo.edu.

Editor: W. A. Petri, Jr.


Infection and Immunity, October 2004, p. 6112-6124, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6112-6124.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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