title: Ever closer to a prophylactic vaccine for HCV.
abstract: BACKGROUND
  With 3 - 4 million new infections occurring annually, hepatitis C virus (HCV) is a major global health problem. There is increasing evidence to suggest that HCV will be highly amenable to a vaccine approach, and despite advances in treatment, a vaccine remains the most cost-effective and realistic means to significantly reduce the worldwide mortality and morbidity associated with persistent HCV infection.
  
  
  METHODS
  In this review we discuss immune responses to HCV during natural infection, and describe how they may inform vaccine design. We introduce the current candidate vaccines for HCV and compare how these fare against the expected requirements of an effective prophylactic HCV vaccine in relation to the breadth, functionality, magnitude and phenotype of the vaccine-induced immune response.
  
  
  CONCLUSIONS
  Although the correlates of immune protection against HCV are not completely defined, we now have vaccine technologies capable of inducing HCV-specific adaptive immune responses to an order of magnitude that are associated with protection during natural infection. The challenge next is to i) establish well-characterised cohorts of people at risk of HCV infection for vaccine efficacy testing and ii) to better understand the correlates of protection in natural history studies. If these can be achieved, a vaccine against HCV appears a realistic goal.
authors: University of Oxford, NDM and Jenner Institute, Peter Medawar Building, South Parks Road, Oxford, OX1 3SY, UK.
authors: Leo
authors: L
authors: Swadling
authors: Paul
authors: P
authors: Klenerman
authors: Eleanor
authors: E
authors: Barnes
mesh_terms: D000818:Animals; D016174:Hepacivirus; D006526:Hepatitis C / Q000517:prevention & control*; D006801:Humans; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage*
chemical_list: D014761:Viral Hepatitis Vaccines
references: Blood. 2007 Sep 15;110(6):1916-23
references: 17510320
references: J Exp Med. 2003 Jun 16;197(12):1645-55
references: 12810686
references: Hepatology. 2007 Mar;45(3):602-13
references: 17326154
references: J Immunol. 2002 Sep 15;169(6):3447-58
references: 12218168
references: J Gen Virol. 2004 Nov;85(Pt 11):3173-3188
references: 15483230
references: Gut. 2011 Nov;60(11):1563-71
references: 21551190
references: Vaccine. 2010 Mar 11;28(12):2397-407
references: 20060945
references: J Exp Med. 1991 May 1;173(5):1099-109
references: 2022921
references: Mol Pharm. 2007 Jan-Feb;4(1):18-32
references: 17274663
references: Clin Vaccine Immunol. 2012 May;19(5):780-6
references: 22441392
references: Science. 2004 Aug 6;305(5685):872-4
references: 15297676
references: N Engl J Med. 2001 Jul 5;345(1):41-52
references: 11439948
references: Immunol Rev. 2011 Jan;239(1):99-108
references: 21198667
references: Sci Transl Med. 2012 Jan 4;4(115):115ra1
references: 22218690
references: Hepatology. 2005 Oct;42(4):828-37
references: 16175596
references: J Virol. 1994 Dec;68(12):8056-63
references: 7966595
references: J Virol. 2007 Aug;81(16):8468-76
references: 17553885
references: Nat Med. 2009 Mar;15(3):293-9
references: 19219024
references: Gut. 2011 Sep;60(9):1284-93
references: 21303914
references: Blood. 2006 Jun 1;107(11):4570-1
references: 16717132
references: Curr Opin Mol Ther. 2009 Aug;11(4):456-62
references: 19649991
references: J Immunol. 2006 Jul 15;177(2):831-9
references: 16818737
references: Hepatology. 2012 Mar;55(3):695-708
references: 22006345
references: J Gen Virol. 2008 Jan;89(Pt 1):1-47
references: 18089727
references: Lancet. 2002 Apr 27;359(9316):1478-83
references: 11988247
references: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6025-30
references: 17392433
references: J Immunol. 2004 May 1;172(9):5553-60
references: 15100298
references: Gut. 2012 May;61 Suppl 1:i1-5
references: 22504915
references: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1294-8
references: 7509068
references: Clin Immunol. 2008 Aug;128(2):133-47
references: 18514579
references: Immunity. 2007 Sep;27(3):393-405
references: 17892848
references: Nature. 1999 Oct 14;401(6754):708-12
references: 10537110
references: J Gen Virol. 2002 Feb;83(Pt 2):369-381
references: 11807230
references: J Infect Dis. 2004 May 15;189(10):1846-55
references: 15122521
references: Vaccine. 2010 Dec 16;29(2):256-65
references: 21029806
references: Nat Rev Immunol. 2002 Sep;2(9):706-13
references: 12209139
references: Gut. 2004 Nov;53(11):1673-81
references: 15479691
references: Gastroenterology. 2007 Feb;132(2):654-66
references: 17258733
references: Nature. 2012 Jan 04;482(7383):89-93
references: 22217938
references: Clin Microbiol Infect. 2011 Feb;17(2):107-15
references: 21091831
references: Eur J Immunol. 1988 Nov;18(11):1653-61
references: 2974420
references: Vaccine. 2005 Feb 18;23(13):1549-58
references: 15694507
references: Gastroenterology. 2003 Jul;125(1):80-8
references: 12851873
references: Gastroenterology. 2010 Sep;139(3):965-74
references: 20621699
references: Nat Med. 2009 Jul;15(7):808-13
references: 19525962
references: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8427-32
references: 17485666
references: J Infect Dis. 2005 Dec 15;192(12):2112-6
references: 16288375
references: Nat Rev Immunol. 2008 Apr;8(4):247-58
references: 18323851
references: Gut. 2012 May;61 Suppl 1:i36-46
references: 22504918
references: Gastroenterology. 2007 Feb;132(2):667-78
references: 17258731
references: J Clin Invest. 1996 Sep 15;98(6):1432-40
references: 8823309
references: Vaccine. 2012 Apr 19;30(19):2943-50
references: 22401867
references: Hepatology. 2006 Sep;44(3):736-45
references: 16941702
references: Immunol Cell Biol. 2011 Mar;89(3):340-5
references: 21301482
references: J Infect Dis. 2011 Sep 1;204(5):811-3
references: 21788452
references: Semin Immunopathol. 2013 Jan;35(1):53-72
references: 22868377
references: J Virol. 2011 Jan;85(1):596-605
references: 20962076
references: Philos Trans R Soc Lond B Biol Sci. 2000 Aug 29;355(1400):1085-92
references: 11186310
references: Gastroenterology. 2010 Jan;138(1):315-24
references: 19782080
references: Expert Opin Biol Ther. 2009 Jul;9(7):805-15
references: 19527105
references: J Virol. 2008 Jan;82(2):966-73
references: 17977972
references: Curr Opin Immunol. 2011 Apr;23(2):244-51
references: 21185706
references: J Virol. 2008 Nov;82(21):10896-905
references: 18753204
references: Gut. 2006 Sep;55(9):1350-9
references: 16905701
references: J Immunol Methods. 2003 Oct 1;281(1-2):65-78
references: 14580882
references: J Virol. 2003 Jan;77(1):382-90
references: 12477843
references: Mol Ther. 2012 Aug;20(8):1633-47
references: 22354374
references: Cytometry A. 2008 Nov;73(11):975-83
references: 18785267
references: PLoS Pathog. 2010 Mar 05;6(3):e1000798
references: 20221423
references: J Clin Microbiol. 2007 Apr;45(4):1102-12
references: 17287328
references: Nat Med. 2008 Jan;14(1):25-7
references: 18064037
references: J Infect Dis. 2011 Sep 15;204(6):837-44
references: 21849281
references: Nat Immunol. 2003 Dec;4(12):1191-8
references: 14625547
references: Hepatology. 2005 Jul;42(1):104-12
references: 15962289
references: J Hepatol. 2011 Jul;55(1):192-206
references: 21284949
references: Sci Transl Med. 2012 Jan 4;4(115):115ra2
references: 22218691
references: Science. 2003 Oct 24;302(5645):659-62
references: 14576438
references: Gastroenterology. 2004 Sep;127(3):924-36
references: 15362047
references: J Immunol. 2011 Aug 1;187(3):1347-57
references: 21715686
references: J Hepatol. 2012 Jul;57(1):9-16
references: 22425625
references: Immunity. 2010 Oct 29;33(4):451-63
references: 21029957
references: Immunity. 2001 Dec;15(6):883-95
references: 11754811
references: J Med Virol. 2006 Feb;78(2):169-77
references: 16372285
references: Hum Vaccin. 2009 Mar;5(3):151-7
references: 19246990
references: J Virol. 2003 Jun;77(11):6305-13
references: 12743287
references: Science. 2000 Sep 22;289(5487):2003
references: 11032545
references: Immunol Rev. 2011 Jan;239(1):109-24
references: 21198668
references: Vaccine. 2004 Jul 29;22(21-22):2717-21
references: 15246602
references: Gut. 2011 Feb;60(2):268-78
references: 20876777
references: J Viral Hepat. 2009 Mar;16(3):156-67
references: 19017255
references: Nat Med. 2006 Feb;12(2):190-7
references: 16462801
references: Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5724-9
references: 21422297
references: J Virol. 2008 Aug;82(15):7492-503
references: 18508900
references: Gastroenterology. 2008 May;134(5):1385-95
references: 18471515
references: J Clin Invest. 2009 Feb;119(2):376-86
references: 19139562
references: Aliment Pharmacol Ther. 2012 Aug;36(4):353-62
references: 22742526
references: Lancet. 2008 Nov 29;372(9653):1881-1893
references: 19012954
references: Nat Med. 2011 Sep 18;17(10):1290-7
references: 21926977
references: Nature. 2005 Aug 18;436(7053):961-6
references: 16107836
references: Immunol Cell Biol. 2001 Dec;79(6):515-36
references: 11903612
references: Addiction. 2007 Sep;102(9):1454-62
references: 17697278
references: Gene Ther. 2006 Jul;13(14):1088-96
references: 16554842
references: Trends Immunol. 2012 Jul;33(7):323-32
references: 22476049
references: Immunity. 2012 Jan 27;36(1):142-52
references: 22265676
references: Nat Med. 2007 Jul;13(7):843-50
references: 17558415
references: Epidemics. 2009 Mar;1(1):47-57
references: 20445816
references: Lancet. 1995 Oct 14;346(8981):1006-7
references: 7475549
references: Med Res Rev. 2009 Nov;29(6):843-66
references: 19378287
references: Eur J Immunol. 1990 May;20(5):1131-5
references: 2113475
references: Vaccine. 2006 May 15;24(20):4343-53
references: 16581161
references: Gastroenterology. 2011 Feb;140(2):686-696.e1
references: 20875418
references: Nature. 2005 Aug 18;436(7053):939-45
references: 16107833
references: Vaccine. 2004 Aug 13;22(23-24):3080-6
references: 15297058
references: Gastroenterology. 2012 Oct;143(4):1048-60.e4
references: 22705008
references: J Exp Med. 2007 Jun 11;204(6):1405-16
references: 17535971
references: Gut. 2012 Aug;61(8):1226-34
references: 21873736
references: Blood. 2006 Jun 15;107(12):4781-9
references: 16467198
references: J Exp Med. 2000 May 1;191(9):1499-512
references: 10790425
references: Science. 1996 Jul 5;273(5271):104-6
references: 8658175
references: Mol Ther. 2004 Oct;10(4):616-29
references: 15451446
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15661-8
references: 12441397
references: Hepatology. 2006 Jul;44(1):126-39
references: 16799989
references: Genes Immun. 2007 Apr;8(3):181-92
references: 17230195
references: Nat Immunol. 2003 Mar;4(3):225-34
references: 12563257
references: Gastroenterology. 1999 Oct;117(4):933-41
references: 10500077
references: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10149-54
references: 15220475
references: Immunity. 1999 Apr;10(4):439-49
references: 10229187
references: J Virol. 2008 Jan;82(2):1047-52
references: 17989176
references: J Virol. 2009 Jan;83(2):1071-82
references: 18971279
references: Science. 2000 Apr 14;288(5464):339-44
references: 10764648
references: Vaccine. 2010 Aug 31;28(38):6367-73
references: 20619382
references: Hepatology. 2012 Aug;56(2):444-54
references: 22331604
references: Semin Immunol. 2004 Jun;16(3):205-12
references: 15130505
references: J Cell Sci. 2006 Dec 15;119(Pt 24):5011-4
references: 17158907