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Nanoparticles encapsulating hepatitis B virus cytosine-phosphate-guanosine induce therapeutic immunity against HBV infection
Shujuan Lv 1,2,
Jun Wang 3,*,
Shuang Dou 3,
Xianzhu Yang 3,
Xiang Ni 1,
Rui Sun 1,
Zhigang Tian 1,*,
Haiming Wei 1,*
Article first published online: 20 DEC 2013
DOI: 10.1002/hep.26654
© 2013 by the American Association for the Study of Liver Diseases
Issue
Hepatology
Hepatology
Volume 59, Issue 2, pages 385–394, February 2014
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How to CiteAuthor InformationPublication History
Author Information
1
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China
2
Department of Microbiology, Anhui Medical University, Hefei, China
3
School of Life Sciences and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China
*Address reprint requests to: Haiming Wei, M.D., Zhigang Tian, Ph.D., or Jun Wang, Ph.D., School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, 230027, Anhui, China. E-mail: [email protected], [email protected], or [email protected]; Fax: +86-551-6360-6783.
Potential conflict of interest: Nothing to report.
Supported by grants from Ministry of Science & Technology of China (973 Basic Science Project 2009CB522403, 2012CB519004) and the Natural Science Foundation of China (#81330071, #30730084).
Infection with hepatitis B virus (HBV) is the most common cause of liver disease worldwide. However, because the current interferon (IFN)-based treatments have toxic side effects and marginal efficacy, improved antivirals are essential. Here we report that unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) from the HBV genome (HBV-CpG) induced robust expression of IFN-α by plasmacytoid dendritic cells (pDCs) in a Toll-like receptor 9 (TLR9)-dependent manner. We also identified inhibitory guanosine-rich ODNs in the HBV genome (HBV-ODN) that are capable of inhibiting HBV-CpG-induced IFN-α production. Furthermore, nanoparticles containing HBV-CpG, termed NP(HBV-CpG), reversed the HBV-ODN-mediated suppression of IFN-α production and also exerted a strong immunostimulatory effect on lymphocytes. Our results suggest that NP(HBV-CpG) can enhance the immune response to hepatitis B surface antigen (HBsAg) and skew this response toward the Th1 pathway in mice immunized with rHBsAg and NP(HBV-CpG). Moreover, NP(HBV-CpG)-based therapy led to the efficient clearance of HBV and induced an anti-HBsAg response in HBV carrier mice. Conclusion: Endogenous HBV-CpG ODNs from the HBV genome induce IFN-α production so that nanoparticle-encapsulated HBV-CpG may act as an HBsAg vaccine adjuvant and may also represent a potent therapeutic agent for the treatment of chronic HBV infection. (Hepatology 2014;59:385–394)
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