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Priming with two DNA vaccines expressing hepatitis C virus NS3 protein targeting dendritic cells elicits superior heterologous protective potential in mice

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Abstract

Development an effective vaccine may offer an alternative preventive and therapeutic strategy against HCV infection. DNA vaccination has been shown to induce robust humoral and cellular immunity and overcome many problems associated with conventional vaccines. In this study, mice were primed with either conventional pVRC-based or suicidal pSC-based DNA vaccines carrying DEC-205-targeted NS3 antigen (DEC-NS3) and boosted with type 5 adenoviral vectors encoding the partial NS3 and core antigens (C44P). The prime boost regimen induced a marked increase in antigen-specific humoral and T-cell responses in comparison with either rAd5-based vaccines or DEC-205-targeted DNA immunization in isolation. The protective effect against heterogeneous challenge was correlated with high levels of anti-NS3 IgG and T-cell-mediated immunity against NS3 peptides. Moreover, priming with a suicidal DNA vaccine (pSC-DEC-NS3), which elicited increased TNF-α-producing CD4+ and CD8+ T-cells against NS3-2 peptides (aa 1245–1461), after boosting, showed increased heterogeneous protective potential compared with priming with a conventional DNA vaccine (pVRC-DEC-NS3). In conclusion, a suicidal DNA vector (pSC-DEC-NS3) expressing DEC-205-targeted NS3 combined with boosting using an rAd5-based HCV vaccine (rAd5-C44P) is a good candidate for a safe and effective vaccine against HCV infection.

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Acknowledgments

The authors thank Dr. Gary Nabel (VRC, NIH, USA) for providing the pVRC vector, Dr. Rod Bremner (University of Toronto, Canada) for providing the pSC vector and Dr. R.M. Steinman (The Rockefeller University, USA) for providing the DEC205 plasmid. This study was supported by the 863 Hi-Tech Research and Development Program of China (2007AA02Z455) and the National Natural Science Foundation of China (81373229).

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Authors and Affiliations

  1. Central Laboratory, Meitan General Hospital, Beijing, 100028, China

    Jie Guan

  2. Key Laboratory of Medical Virology, Ministry of Health; National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, ChangPing District, Beijing, 102206, China

    Jie Guan, Yao Deng, Hong Chen, Xiao Yin, Yang Yang & Wenjie Tan

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  1. Jie Guan
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  2. Yao Deng
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  4. Xiao Yin
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Corresponding author

Correspondence to Wenjie Tan.

Additional information

J. Guan and Y. Deng are co-first authors.

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Table S1. The NS3 peptide pools used in this study (DOC 29 kb)

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Guan, J., Deng, Y., Chen, H. et al. Priming with two DNA vaccines expressing hepatitis C virus NS3 protein targeting dendritic cells elicits superior heterologous protective potential in mice. Arch Virol 160, 2517–2524 (2015). https://doi.org/10.1007/s00705-015-2535-7

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  • DOI: https://doi.org/10.1007/s00705-015-2535-7

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