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Infection and Immunity, May 2004, p. 2635-2647, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2635-2647.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cross-Reactivity of Schistosoma mansoni Cytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Claudia Carvalho-Queiroz,¹ Rosemary Cook,¹ Ching C. Wang,^2, Rodrigo Correa-Oliveira,³ Nicola A. Bailey,^4, Nejat K. Egilmez,^1, Edith Mathiowitz,⁴ and Philip T. LoVerde^1*

Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences,¹ Division of Gastroenterology, State University of New York, Buffalo, New York 14214,² Laboratory of Immunology, Centro de Pesquisas Rene Rachou, Fundacao Oswaldo Cruz, Belo Horizonte, Brazil,³ Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912⁴

Received 27 October 2003/ Returned for modification 24 December 2003/ Accepted 3 February 2004

Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.

Editor: W. A. Petri, Jr.

Present address: Yavapai Medical Center, Prescott, AZ 86301.

Present address: AstraZeneca Pharmaceuticals, Macclesfield, Cheshire, SK10 2NA England.

Present address: J.G. Brown Cancer Center and Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202.

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• Cook, R. M., Carvalho-Queiroz, C., Wilding, G., LoVerde, P. T. (2004). Nucleic Acid Vaccination with Schistosoma mansoni Antioxidant Enzyme Cytosolic Superoxide Dismutase and the Structural Protein Filamin Confers Protection against the Adult Worm Stage. Infect. Immun. 72: 6112-6124 [Abstract] [Full Text]