Therapeutic vaccines and immune-based therapies for the treatment of chronic hepatitis B: Perspectives and challenges

被引:168
作者
Michel, Marie-Louise [1 ,2 ,3 ]
Deng, Qiang [4 ]
Mancini-Bourgine, Maryline [1 ,2 ]
机构
[1] Inst Pasteur, Dept Virol, Lab Pathogenese Virus Hepatite B, F-75015 Paris, France
[2] INSERM, Fac Med Paris Descartes, Ctr Rech Croissance & Signalisat, U845, F-75015 Paris, France
[3] AP HP, Paris, France
[4] Inst Pasteur, Unit Tumor Virol, Shanghai 200025, Peoples R China
关键词
Hepatitis B; Chronic infection; Immunotherapy; Vaccine; DNA vaccine; T-cell therapy; Clinical trial; REGULATORY T-CELLS; SURFACE-ANTIGEN HBSAG; DENDRITIC CELLS; TRANSGENIC MICE; COMBINATION THERAPY; VIRUS SUPPRESSION; CLINICAL-TRIAL; NASAL VACCINE; CORE ANTIGEN; DNA VACCINE;
D O I
10.1016/j.jhep.2010.12.031
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
The treatment of chronic hepatitis B virus (HBV) infection has greatly improved over the last 10 years, but alternative treatments are still needed. Therapeutic vaccination is a promising new strategy for controlling chronic infection. However, this approach has not been as successful as initially anticipated for chronic hepatitis B. General impairment of the immune responses generated during persistent HBV infection, with exhausted T cells not responding correctly to therapeutic vaccination, is probably responsible for the poor clinical responses observed to date. Intensive research efforts are now focusing on increasing the efficacy of therapeutic vaccination without causing liver disease. Here we describe new approaches to use with therapeutic vaccination, in order to overcome the inhibitory mechanisms impairing immune responses. We also describe innovative strategies for generating functional immune responses and inducing sustained control of this persistent infection. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1286 / 1296
页数:11
相关论文
共 86 条
[1]
Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen [J].
Aguilar, JC ;
Lobaina, Y ;
Muzio, V ;
García, D ;
Pentón, E ;
Iglesias, E ;
Pichardo, D ;
Urquiza, D ;
Rodríguez, D ;
Silva, D ;
Petrovsky, N ;
Guillén, G .
IMMUNOLOGY AND CELL BIOLOGY, 2004, 82 (05) :539-546
[2]
Akbar SM, 2010, J VIRAL HEPAT 0517
[3]
Safety and efficacy of hepatitis B surface antigen-pulsed dendritic cells in human volunteers [J].
Akbar, SMF ;
Furukawa, S ;
Onji, M ;
Murata, Y ;
Niya, T ;
Kanno, S ;
Murakami, H ;
Horiike, N .
HEPATOLOGY RESEARCH, 2004, 29 (03) :136-141
[4]
Akbar SMF, 1997, J HEPATOL, V26, P131
[5]
Combination Therapy with Antiviral Drugs and Hepatitis B Vaccine in Incidentally-Detected and Asymptomatic Chronic Hepatitis Virus B Carriers at Bangladesh [J].
Al-Mahtab, Mamun ;
Rahman, Salimur ;
Akbar, Sheikh Mohammad Fazle ;
Khan, Sakirul Islam ;
Uddin, Helal ;
Karim, Fazal ;
Ahmed, Faroque .
VIRAL IMMUNOLOGY, 2010, 23 (03) :335-338
[6]
[Anonymous], HEPATOL INT
[7]
Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[8]
Protection or damage: a dual role for the virus-specific cytotoxic T lymphocyte response in hepatitis B and C infection? [J].
Bertoletti, A ;
Maini, MK .
CURRENT OPINION IN MICROBIOLOGY, 2000, 3 (04) :387-392
[9]
Bertoletti Antonio, 2009, Expert Rev Gastroenterol Hepatol, V3, P561, DOI 10.1586/egh.09.48
[10]
Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens [J].
Betancourt, Aristides Aguilar ;
Delgado, C. A. Gonzalez ;
Estevez, Z. Cinza ;
Martinez, J. Cabrera ;
Rios, G. Veliz ;
Aureoles-Rosello, S. R. Moreno ;
Zaldivar, R. Aleman ;
Guzman, M. Alonso ;
Baile, N. Figueroa ;
Reyes, P. A. Dias ;
Ruano, L. Olivera ;
Fernandez, A. Correa ;
Lobaina-Matos, Y. ;
Fernandez, A. Delahanty ;
Madrazo, A. I. Juvier ;
Martinez, M. I. Alonso ;
Banos, M. Lago ;
Alvarez, N. Puble ;
Baldo, M. David ;
Mestre, R. E. Soto ;
Perez, M. V. Perez ;
Martinez, M. E. Pena ;
Escobar, D. Acosta ;
Guanche, M. J. Cerna ;
Caceres, L. Mila ;
Betancourt, R. Sanchez ;
Rando, E. Hardy ;
Nieto, G. E. Guillen ;
Gonzalez, V. L. Muzio ;
Rubido, J. C. Aguilar .
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2007, 11 (05) :394-401