Prospects for prophylactic and therapeutic vaccines against the hepatitis C viruses

被引:140
作者
Houghton, Michael [1 ]
机构
[1] Univ Alberta, Dept Med Microbiol & Immunol, Li Ka Shing Inst Virol, Rexall Ctr Hlth Res,Katz Grp 6010, Edmonton, AB T6G 2E1, Canada
关键词
hepatitis C virus; vaccine; HCV prophylactic vaccine; HCV therapeutic vaccine; HCV immunology; T-CELL RESPONSES; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEINS; IMMUNE-RESPONSES; HEALTHY-VOLUNTEERS; EFFECTOR FUNCTION; NATURAL-HISTORY; VIRAL CLEARANCE; INFECTION; HCV;
D O I
10.1111/j.1600-065X.2010.00977.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Encouraging efficacy data have been obtained in the hepatitis C virus (HCV) chimpanzee model using prophylactic vaccines comprising adjuvanted recombinant envelope gpE1/gpE2 glycoproteins or prime/boost immunization regimens using defective adenoviruses and plasmid DNA expressing non-structural genes. While usually not resulting in sterilizing immunity after experimental challenge, the progression to chronic, persistent infection (which is responsible for HCV-associated pathogenicity in human) is inhibited. These and other vaccine candidates are in clinical development for both prophylactic as well as possible therapeutic applications. Given that other vaccines tested in the chimpanzee model may be possibly increasing the rate of chronicity, it is very important that this model continues to be available and used prior to initiation of clinical development. Several vaccine monotherapy trials in chronically infected HCV patients are resulting in small declines in viral load, suggesting that in future, combining vaccination with antiviral drug treatment may be beneficial.
引用
收藏
页码:99 / 108
页数:10
相关论文
共 70 条
[1]   In vivo electroporation enhances the immunogenicity of hepatitis C virus nonstructural 3/4A DNA by increased local DNA uptake, protein expression, inflammation, and infiltration of CD3+ T cells [J].
Ahlen, Gustaf ;
Soderholm, Jonas ;
Tjelle, Torunn ;
Kjeken, Rune ;
Frelin, Lars ;
Hoglund, Urban ;
Blomberg, Pontus ;
Fons, Michael ;
Mathiesen, Iacob ;
Sallberg, Matti .
JOURNAL OF IMMUNOLOGY, 2007, 179 (07) :4741-4753
[2]   Patient HLA-DRB1*and-DQB1*allele and haplotype association with hepatitis C virus persistence and clearance [J].
Ali, Lubna ;
Mansoor, Atika ;
Ahmad, Nafees ;
Siddiqi, Saima ;
Mazhar, Kehkashan ;
Muazzam, Ambreen G. ;
Qamar, Raheel ;
Khan, Khalid M. .
JOURNAL OF GENERAL VIROLOGY, 2010, 91 :1931-1938
[3]   HCV natural history: The retrospective and prospective in perspective [J].
Alter, HJ .
JOURNAL OF HEPATOLOGY, 2005, 43 (04) :550-552
[4]   Epidemiology of hepatitis C virus infection [J].
Alter, Miriam J. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (17) :2436-2441
[5]   An interplay between hypervariable region 1 of the Hepatitis C Virus E2 glycoprotein, the scavenger receptor BI, and high-density lipoprotein promotes both enhancement of infection and protection against neutralizing antibodies [J].
Bartosch, B ;
Verney, G ;
Dreux, M ;
Donot, P ;
Morice, Y ;
Penin, F ;
Pawlotsky, JM ;
Lavillette, D ;
Cosset, FL .
JOURNAL OF VIROLOGY, 2005, 79 (13) :8217-8229
[6]   T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection [J].
Boettler, T ;
Spangenberg, HC ;
Neumann-Haefelin, C ;
Panther, E ;
Urbani, S ;
Ferrari, C ;
Blum, HE ;
von Weizsäcker, F ;
Thimme, R .
JOURNAL OF VIROLOGY, 2005, 79 (12) :7860-7867
[7]   Adaptive immune responses in acute and chronic hepatitis C virus infection [J].
Bowen, DG ;
Walker, CM .
NATURE, 2005, 436 (7053) :946-952
[8]   Studies of hepatitis C virus in chimpanzees and their importance for vaccine development [J].
Bukh, J ;
Forns, X ;
Emerson, SU ;
Purcell, RH .
INTERVIROLOGY, 2001, 44 (2-3) :132-142
[9]   Previously infected chimpanzees are not consistently protected against reinfection or persistent infection after reexposure to the identical hepatitis C virus strain [J].
Bukh, Jens ;
Thimme, Robert ;
Meunier, Jean-Christophe ;
Faulk, Kristina ;
Spangenberg, Hans Christian ;
Chang, Kyong-Mi ;
Satterfield, William ;
Chisari, Francis V. ;
Purcell, Robert H. .
JOURNAL OF VIROLOGY, 2008, 82 (16) :8183-8195
[10]   Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders [J].
Carneiro, Valdirene Leao ;
Lemaire, Denise C. ;
Bendicho, Maria Teresita ;
Souza, Sabrina L. ;
Cavalcante, Lourianne Nascimento ;
Angelo, Ana Luisa ;
Freire, Songeli Menezes ;
Cardeal Mendes, Carlos Mauricio ;
Santana, Nelma ;
Costa Lyra, Luiz G. ;
Lyra, Andre Castro .
LIVER INTERNATIONAL, 2010, 30 (04) :567-573