Current progress in development of hepatitis C virus vaccines

被引:129
作者
Liang, T. Jake [1 ]
机构
[1] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA
关键词
T-CELL RESPONSES; ADAPTIVE IMMUNE-RESPONSES; NEUTRALIZING ANTIBODIES; SPONTANEOUS CLEARANCE; GENETIC-VARIATION; HCV INFECTION; CHIMPANZEES; VACCINATION; ANTIGEN; HIV;
D O I
10.1038/nm.3183
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Despite major advances in the understanding and treatment of hepatitis C, a preventive vaccine remains elusive. The marked genetic diversity and multiple mechanisms of persistence of hepatitis C virus, combined with the relatively poor immune response of the infected host against the virus, are major barriers. The lack of robust and convenient model systems further hampers the effort to develop an effective vaccine. Advances in our understanding of virus-host interactions and protective immunity in hepatitis C virus infection provide an important roadmap to develop potent and broadly directed vaccine candidates targeting both humoral and cellular immune responses. Multiple approaches to generating and testing viral immunogens have met with variable success. Several candidates have advanced to clinical trials based on promising results in chimpanzees. The ultimate path to a successful preventive vaccine requires comprehensive evaluations of all aspects of protective immunity, innovative application of state-of-the-art vaccine technology and properly designed vaccine trials that can affirm definitive endpoints of efficacy.
引用
收藏
页码:869 / 878
页数:10
相关论文
共 121 条
[1]   Characterization of low- and very-low-density hepatitis C virus RNA-containing particles [J].
André, P ;
Komurian-Pradel, F ;
Deforges, S ;
Perret, M ;
Berland, JL ;
Sodoyer, M ;
Pol, S ;
Bréchot, C ;
Paranhos-Baccalà, G ;
Lotteau, V .
JOURNAL OF VIROLOGY, 2002, 76 (14) :6919-6928
[2]  
[Anonymous], CHIMP BIOM BEH RES A
[3]   The prevalence of hepatitis C virus infection in the United States, 1999 through 2002 [J].
Armstrong, Gregory L. ;
Wasley, Annemarie ;
Simard, Edgar P. ;
McQuillan, Geraldine M. ;
Kuhnert, Wendi L. ;
Alter, Miriam J. .
ANNALS OF INTERNAL MEDICINE, 2006, 144 (10) :705-714
[4]   Lessons from Chimpanzee-based Research on Human Disease: The Implications of Genetic Differences [J].
Bailey, Jarrod .
ATLA-ALTERNATIVES TO LABORATORY ANIMALS, 2011, 39 (06) :527-540
[5]   SELECTIVE KILLING OF HEPATITIS-B ENVELOPE ANTIGEN-SPECIFIC B-CELLS BY CLASS-I-RESTRICTED, EXOGENOUS ANTIGEN-SPECIFIC LYMPHOCYTES-T [J].
BARNABA, V ;
FRANCO, A ;
ALBERTI, A ;
BENVENUTO, R ;
BALSANO, F .
NATURE, 1990, 345 (6272) :258-260
[6]  
Barnes E., 2012, SCI TRANSL MED, V4, p115ra1
[7]   Mouse models for the study of HCV infection and virus-host interactions [J].
Barth, Heidi ;
Robinet, Eric ;
Liang, T. Jake ;
Baumert, Thomas F. .
JOURNAL OF HEPATOLOGY, 2008, 49 (01) :134-142
[8]   Both Innate and Adaptive Immunity Mediate Protective Immunity Against Hepatitis C Virus Infection in Chimpanzees [J].
Barth, Heidi ;
Rybczynska, Jolanta ;
Patient, Romuald ;
Choi, Youkyung ;
Sapp, Ronda K. ;
Baumert, Thomas F. ;
Krawczynski, Kris ;
Liang, T. Jake .
HEPATOLOGY, 2011, 54 (04) :1135-1148
[9]   Adaptive immune responses in acute and chronic hepatitis C virus infection [J].
Bowen, DG ;
Walker, CM .
NATURE, 2005, 436 (7053) :946-952
[10]   Mutational escape from CD8+ T cell immunity:: HCV evolution, from chimpanzees to man [J].
Bowen, DG ;
Walker, CM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (11) :1709-1714