TY - JOUR
T1 - Clearing persistent extracellular antigen of hepatitis B virus
T2 - An immunomodulatory strategy to reverse tolerance for an effective therapeutic vaccination
AU - Zhu, Danming
AU - Liu, Longchao
AU - Yang, Dan
AU - Fu, Sherry
AU - Bian, Yingjie
AU - Sun, Zhichen
AU - He, Junming
AU - Su, Lishan
AU - Zhang, Liguo
AU - Peng, Hua
AU - Fu, Yang Xin
N1 - Funding Information:
This work was supported by the National Key Basic Research Program of China (Grants 2012CB910203, 2012CB519000, and 2009CB522502 to Y.-X.F. and H.P.), the National Grand Program on Key Infectious Disease (Grants 2012ZX10002006 and 2013ZX10002001-001-003 to Y.-X.F. and H.P.), the National Nature and Science Foundation of China (Grant 81172814 to H.P.), the Ministry of Science and Technology (Grants 2009CB522507, 2010-Biols-CAS-0201, and KSCX20YW-R-50 to L.Z.), the Ministry of Health (Grant 2011ZX10004503-007 to L.Z. and L.S.), and by the National Institutes of Health (Grant R01AI095097 to L.S. and Y.-X.F.).
Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection has been challenging because of HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface Ag in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg Ab in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral Ag with neutralizing Abs followed by vaccination.
AB - Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection has been challenging because of HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface Ag in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg Ab in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral Ag with neutralizing Abs followed by vaccination.
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U2 - 10.4049/jimmunol.1502061
DO - 10.4049/jimmunol.1502061
M3 - Article
C2 - 26936879
AN - SCOPUS:84962597523
SN - 0022-1767
VL - 196
SP - 3079
EP - 3087
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -