CVI Accepts, published online ahead of print on 7 October 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00231-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

DNA vaccination by electroporation and boosting with recombinant proteins enhances efficacy of DNA vaccines for schistosomiasis japonica.

Yang Dai, Yinchang Zhu^*, Donald A. Harn, Xiaoting Wang, Jianxia Tang, Song Zhao, Fei Lu, and Xiaohong Guan

Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Lab on Molecular Biology of Parasites, Jiangsu Provincial Key Subject on Parasitic Diseases, Wuxi 214064, China; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, USA; Key Laboratory of Antibody Technique, Ministry of Health, Nanjing Medical University, Nanjing 210029, China

^* To whom correspondence should be addressed. Email: yczhu2006{at}yahoo.com.cn.

Schistosomiasis japonica is an endemic, zoonotic disease of major public health importance in China. Control programs combining chemtherapy and snail killing have not been able to block transmission of infection in lakes and marsh regions. Vaccination is needed as a complimentary approach to the ongoing control programs. In the present study, we wanted to determine if vaccine efficacy of DNA vaccines encoding 23kDa tetraspanin membrane protein (SjC23), triose phosphate isomerase (SjCTPI) and 6-fold repeated genes of the complementarity determining region 3 (CDR3) in H chain of NP30 could be enhanced by boosting via electroporation in vivo and/or with cocktail protein vaccines. Mice vaccinated with cocktail DNA vaccines showed significant worm reduction of 32.88% (P < 0.01) and egg reduction of 36.20% (P < 0.01). Vaccine efficacy was enhanced when boosted with cocktail protein vaccines; adult worm and liver egg burdens were reduced 45.35% and 48.54% respectively. Nearly identical results were obtained in mice boosted by electroporation in vivo, with adult worm and egg burdens reduced by 45.00% and 50.88% respectively. The addition of a protein vaccine boost to this regimen further elevated efficacy to approximately 60% for adult worm burden, and greater than 60% for liver egg reduction. The levels of IL-2, IFN- and the ratios of IgG2a/IgG1, clearly showed that cocktail DNA vaccines induced CD4+ Th1-type responses. Both boosting via electroporation, or with recombinant proteins significantly increased associated immune responses over that seen in mice vaccinated solely with DNA vaccines. Thus, schistosome DNA vaccine efficacy was significantly enhanced via boosting by electroporation in vivo and/or protein vaccines.