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Synergistic enhancement of immunogenicity and protection in mice against Schistosoma japonicum with codon optimization and electroporation delivery of SjTPI DNA vaccines
Authors:Yinchang Zhu  Fei Lu  Yang Dai  Xiaoting Wang  Jianxia Tang  Song Zhao  Chun Zhang  Hui Zhang  Shan Lu  Shixia Wang
Affiliation:1. Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, 117 Yangxiang Meiyuan, Wuxi 214064, Jiangsu, China;2. Yangzhou Health Inspection Institute, Yangzhou 225002, China;3. Jiangsu Key Laboratory of Infectious Diseases, Department of Infectious Diseases, Nanjing 210029, China;4. China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;5. Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester 01605, USA
Abstract:Schistosomiasis is an endemic, zoonotic parasitic disease caused by Schistosoma japonicum that remains a public health concern and an effective vaccine is needed. Triose-phosphate isomerase from S. japonicum is a promising schistosome vaccine antigen shown to be immunogenic when delivered as a DNA vaccine, however, the previous S. japonicum triose-phosphate isomerase (SjTPI) DNA vaccine needs to be further optimized to achieve higher protection. In the current study, codon optimization of SjTPI DNA insert, combined with electroporation but not with the addition of a tPA leader or heat-shock protein in-frame with the SjTPI gene insert, enhanced Th1-type antibody and cytokine production and most significantly, achieved great than 50% reduction of infection against challenge with S. japonicum cercariae, a major milestone in S. japonicum vaccine development. Our results suggest that the combination of a codon optimized vaccine design and an efficient vaccine delivery system can greatly improve the potential of a SjTPI DNA vaccine as a viable schistosome vaccine candidate.
Keywords:Schistosoma japonicum   DNA vaccine   Optimization
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