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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 7
Jul.  2016
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Article Contents

New immunotherapeutic strategies for chronic hepatitis B

DOI: 10.3969/j.issn.1001-5256.2016.07.042
  • Published Date: 2016-07-20
  • Chronic hepatitis B( CHB) is one of the most important infectious diseases around the world. Currently,interferon and nucleos( t) ide analogues are the main drugs for CHB and have good therapeutic efficacy,but the ultimate goal of eliminating hepatitis B virus( HBV) in human body has not been achieved. Therefore,it is of vital importance to explore new therapeutic strategies and develop new drugs for CHB. Persistent HBV infection is closely associated with human body's immune status,and studies have shown that immunotherapy may help to cure CHB. With reference to CHB patients' immune status,this article reviews the research advances in new immunotherapeutic strategies including Toll- like receptor agonists,cell therapy,and therapeutic vaccines.

     

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  • [1]Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B:a 2015 update[J].J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015年更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.
    [2]LI J,ZHUANG H.Advances in the epidemiology of viral hepatitis[J].Chin Hepatol,2012,17(1):2-5.(in Chinese)李杰,庄辉.病毒性肝炎流行病学进展[J].肝脏,2012,17(1):2-5.
    [3]SEKI E,BRENNER DA.Toll-like receptors and adaptor molecules in liver disease:update[J].Hepatology,2008,48(1):322-335.
    [4]SCHWABE RF,SEKI E,BRENNER DA.Toll-like receptor signaling in the liver[J].Gastroenterology,2006,130(6):1886-1900.
    [5]WU J,MENG Z,JIANG M,et al.Hepatitis B virus suppresses toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells[J].Hepatology,2009,49(4):1132-1140.
    [6]BECKEBAUM S,CICINNATI VR,ZHANG X,et al.Hepatitis Bvirus-induced defect of monocyte-derived dendritic cells leads to impaired T helper type 1 response in vitro:mechanisms for viral immune escape[J].Immunology,2003,109(4):487-495.
    [7]WOLTMAN AM,OP den BROUW ML,BIESTA PJ,et al.Hepatitis B virus lacks immune activating capacity,but actively inhibits plasmacytoid dendritic cell function[J].PLoS One,2011,6(1):e15324.
    [8]BERTOLETTI A,GEHRING A.Immune response and tolerance during chronic hepatitis B virus infection[J].Hepatol Res,2007,37(Suppl 3):s331-s338.
    [9]XU L,DA L,PLOUFFE SW,et al.Molecular basis of transcriptional fidelity and DNA lesion-induced transcriptional mutagenesis[J].DNA Repair(Amst),2014,19:71-83.
    [10]LI X,LIU X,TIAN L,et al.Cytokine-mediated immunopathogenesis of hepatitis B virus infections[J].Clin Rev Allergy Immunol,2016,50(1):41-54.
    [11]ZHANG Z,ZHANG JY,WANG LF,et al.Immunopathogenesis and prognostic immune markers of chronic hepatitis B virus infection[J].J Gastroenterol Hepatol,2012,27(2):223-230.
    [12]MAINI MK,BONI C,LEE CK,et al.The role of virus-specific CD8+cells in liver damage and viral control during persistent hepatitis B virus infection[J].J Exp Med,2000,191(8):1269-1280.
    [13]YE B,LIU X,LI X,et al.T-cell exhaustion in chronic hepatitis B infection:current knowledge and clinical significance[J].Cell Death Dis,2015,6(3):e1694.
    [14]LA CAVA A,van KAER L,FU-DONG-SHI.CD4+CD25+Tregs and NKT cells:regulators regulating regulators[J].Trends Immunol,2006,27(7):322-327.
    [15]WU J,CHEN MF,XIA YC,et al.Toll-like receptor dependent innate immune responses by primary mouse hepatocytes and its control of HBV replication[J].Chin J Hepatol,2011,19(11):838-842.(in Chinese)吴珺,陈明发,夏幼辰,等.Toll样受体介导小鼠原代肝细胞产生的天然免疫应答及其对乙型肝炎病毒复制的抑制作用[J].中华肝脏病杂志,2011,19(11):838-842.
    [16]XU YY,CHEN L,ZHOU JM,et al.Inhibitory effect of dsRNATLR3 agonist in a rat hepatocellular carcinoma model[J].Mol Med Rep,2013,8(4):1037-1042.
    [17]XU YY,CHEN L,WANG GL,et al.A synthetic dsRNA,as a TLR3 pathwaysynergist,combined with sorafenib suppresses HCCin vitro and in vivo[J].BMC Cancer,2013,13:527.
    [18]PURCELL RH,LONDON WT,McA ULIFFE VJ,et al.Modification of chronic hepatitis-B virus infection in chimpanzees by administration of an interferon inducer[J].Lancet,1976,2(7989):757-761.
    [19]WU J,HUANG S,ZHAO X,et al.Poly(I∶C)treatment leads to interferon-dependent clearance of hepatitis B virus in a hydrodynamic injection mouse model[J].J Virol,2014,88(18):10421-10431.
    [20]ROBINSON RA,DEVITA VT,LEVY HB,et al.A phaseⅠ-Ⅱtrial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors[J].J Natl Cancer Inst,1976,57(3):599-602.
    [21]IJICHI K,MITAMURA K,IDA S,et al.In vivo antiviral effects of mismatched double-stranded RNA on duck hepatitis B virus[J].JMed Virol,1994,43(2):161-165.
    [22]LANFORD RE,GUERRA B,CHAVEZ D,et al.GS-9620,an oral agonist of Toll-like receptor-7,induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees[J].Gastroenterology,2013,144(7):1508-1517.
    [23]MENNE S,TUMAS DB,LIU KH,et al.Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B[J].J Hepatol,2015,62(6):1237-1245.
    [24]LOPATIN U,WOLFGANG G,TUMAS D,et al.Safety,pharmacokinetics and pharmacodynamics of GS-9620,an oral Toll-like receptor 7 agonist[J].Antivir Ther,2013,18(3):409-418.
    [25]GANE EJ,LIM YS,GORDON SC,et al.The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection[J].J Hepatol,2015,63(2):320-328.
    [26]JO J,TAN AT,USSHER JE,et al.Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver[J].PLoS Pathog,2014,10(6):e1004210.
    [27]HEDAYAT M,NETEA MG,REZAEI N.Targeting of Toll-like receptors:a decade of progress in combating infectious diseases[J].Lancet Infect Dis,2011,11(9):702-712.
    [28]HALPERINA SA,WARDB B,COOPERC C,et al.Comparison of safety and immunogenicity of two doses of investigational hepatitis Bvirus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age[J].Vaccine,2012,30(15):2556-2563.
    [29]COOPER CL,DAVIS HL,MORRIS ML,et al.CPG 7909,an immunostimulatory TLR9 agonist oligodeoxynucleotide,as adjuvant to Engerix-B HBV vaccine in healthy adults:a double-blind phaseⅠ/Ⅱstudy[J].J Clin Immunol,2004,24(6):693-701.
    [30]SIEGRISTA CA,PIHLGRENA M,TOUGNEA C,et al.Co-administration of Cp G oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response[J].Vaccine,2004,23(5):615-622.
    [31]HALPERIN SA,DOBSONB S,McN EIL S,et al.Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults[J].Vaccine,2006,24(1):20-26.
    [32]JACQUES P,MOENS G,DESOMBERE I,et al.The immunogenicity and reactogenicity profile of a candidate hepatitis B vaccine in an adult vaccine non-responder population[J].Vaccine,2002,20(31-32):3644-3649.
    [33]SURQUIN M,TIELEMANS C,NORTIER J,et al.Anti-HBs antibody persistence following primary vaccination with an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency[J].Hum Vaccin,2011,7(9):913-918.
    [34]KUNDI M.New hepatitis B vaccine formulated with an improved adjuvant system[J].Expert Rev Vaccines,2007,6(2):133-140.
    [35]GRZEGORZEWSKA AE.Hepatitis B vaccination in chronic kidney disease patients:a call for novel vaccines[J].Expert Rev Vaccines,2014,13(11):1317-1326.
    [36]di PASQUALE A,de RIDDER M,van DER MEEREN O.Hepatitis Bvirus vaccine in chronic kidney diseases:improved immunogenicity by adjuvants?Limits of a meta-analysis[J].Vaccine,2012,30(38):5586.
    [37]BOHNE F,CHMIELEWSKI M,EBERT G,et al.T cells redirected against hepatitis B virus surface proteins eliminate infected hepatocytes[J].Gastroenterology,2008,134(1):239-247.
    [38]KREBS K,BTTINGER N,HUANG LR,et al.T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice[J].Gastroenterology,2013,145(2):456-465.
    [39]SHI M,FU J,SHI F,et al.Transfusion of autologous cytokineinduced killer cells inhibits viral replication in patients with chronic hepatitis B virus infection[J].Clin Immunol,2009,132(1):43-54.
    [40]YAO X,ZHENG B,ZHOU J,et al.Therapeutic effect of hepatitis Bsurface antigen-antibody complex is associated with cytolytic and non-cytolytic immune responses in hepatitis B patients[J].Vaccine,2007,25(10):1771-1779.
    [41]XU DZ,WANG XY,SHEN XL,et al.Results of a phaseⅢclinical trial with an HBsA g-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients:experiences and findings[J].J Hepatol,2013,59(3):450-456.
    [42]LI J,GE J,REN S,et al.Hepatitis B surface antigen(HBsA g)and core antigen(HBcA g)combine Cp G oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection[J].Vaccine,2015,33(35):4247-4254.
    [43]LE GUERHIER F,THERMET A,GUERRET S,et al.Antiviral effect of adefovir in combination with a DNA vaccine in the duck hepatitis B virus infection model[J].J Hepatol,2003,38(3):328-334.
    [44]LOIRAT D,MANCINI-BOURGINE M,ABASTADO JP,et al.HBsA g/HLA-A2 transgenic mice:a model for T cell tolerance to hepatitis B surface antigen in chronic hepatitis B virus infection[J].Int Immunol,2003,15(10):1125-1136.
    [45]SAADE F,BURONFOSSE T,GUERRET S,et al.In vivo infectivity of liver extracts after resolution of hepadnaviral infection following therapy associating DNA vaccine and cytokine genes[J].J Viral Hepat,2013,20(4):e56-e65.
    [46]THERMET A,BURONFOSSE T,WERLE-LAPOSTOLLE B,et al.DNA vaccination in combination or not with lamivudine treatment breaks humoral immune tolerance and enhances cccD NA clearance in the duck model of chronic hepatitis B virus infection[J].JGen Virol,2008,89(Pt 5):1192-1201.
    [47]YANG FQ,YU YY,WANG GQ,et al.A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy[J].J Viral Hepat,2012,19(8):581-593.
    [48]CAROTENUTO P,ARTSEN A,NIESTERS HG,et al.In vitro use of autologous dendritic cells improves detection of T cell responses to hepatitis B virus(HBV)antigens[J].J Med Virol,2009,81(2):332-339.
    [49]LUO J,LI J,CHEN RL,et al.Autologus dendritic cell vaccine for chronic hepatitis B carriers:a pilot,open label,clinical trial in human volunteers[J].Vaccine,2010,28(13):2497-2504.
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