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• W2894067555 abstract "Risk factors for hepatitis C virus (HCV) infection vary, and there were an estimated 1.75 million new cases worldwide in 2015. The World Health Organization aims for a 90% reduction in new HCV infections by 2030. An HCV vaccine would prevent transmission, regardless of risk factors, and significantly reduce the global burden of HCV-associated disease. Barriers to development include virus diversity, limited models for testing vaccines, and our incomplete understanding of protective immune responses. Although highly effective vaccines could prevent infection altogether, immune responses that increase the rate of HCV clearance and prevent chronic infection may be sufficient to reduce disease burden. Adjuvant envelope or core protein and virus-vectored nonstructural antigen vaccines have been tested in healthy volunteers who are not at risk for HCV infection; viral vectors encoding nonstructural proteins are the only vaccine strategy to be tested in at-risk individuals. Despite development challenges, a prophylactic vaccine is necessary for global control of HCV. Risk factors for hepatitis C virus (HCV) infection vary, and there were an estimated 1.75 million new cases worldwide in 2015. The World Health Organization aims for a 90% reduction in new HCV infections by 2030. An HCV vaccine would prevent transmission, regardless of risk factors, and significantly reduce the global burden of HCV-associated disease. Barriers to development include virus diversity, limited models for testing vaccines, and our incomplete understanding of protective immune responses. Although highly effective vaccines could prevent infection altogether, immune responses that increase the rate of HCV clearance and prevent chronic infection may be sufficient to reduce disease burden. Adjuvant envelope or core protein and virus-vectored nonstructural antigen vaccines have been tested in healthy volunteers who are not at risk for HCV infection; viral vectors encoding nonstructural proteins are the only vaccine strategy to be tested in at-risk individuals. Despite development challenges, a prophylactic vaccine is necessary for global control of HCV. Eleanor BarnesView Large Image Figure ViewerDownload Hi-res image Download (PPT)Andrea L. CoxView Large Image Figure ViewerDownload Hi-res image Download (PPT) The advent of all oral, interferon-sparing direct-acting antivirals (DAAs) that cure hepatitis C virus (HCV) infection has transformed treatment, particularly in high-income countries. Although DAAs have fueled optimism for global control, several limitations of treatment make development of a preventive vaccine necessary to achieve that goal. HCV infections are rarely symptomatic before the onset of advanced liver disease, and HCV screening is rare in most parts of the world, so most persons with HCV infection are not identified.1Gravitz L. Introduction: a smouldering public-health crisis.Nature. 2011; 474: S2-S4Crossref PubMed Scopus (121) Google Scholar In addition, the cost of and practical aspects to delivering therapy result in only a subset of those diagnosed being treated. HCV treatment has been decreasing globally since its peak in 2015, as the HCV-infected people easiest to access have been treated, leaving those more difficult to access without treatment (John McHutchinson and Diana Brainard, Gilead Sciences, personal communication; 2018). Some treated individuals have developed resistance to DAAs, and transmission of resistant HCV variants was documented in clinical trials before DAAs were even approved.2Franco S. Tural C. Nevot M. et al.Detection of a sexually transmitted hepatitis C virus protease inhibitor-resistance variant in a human immunodeficiency virus-infected homosexual man.Gastroenterology. 2014; 147: 599-601.e1Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar With expansion of treatment to patients less able to take medication reliably, antiviral resistance is likely to become more common. Furthermore, liver disease can progress and cancer can develop despite cure of the HCV infection in patients with cirrhosis. So, treatment does not eliminate all of the consequences of HCV infection and prevention of chronic infection offers significant advantages over treatment. Despite increased cure rates with DAA, HCV elimination continues to be difficult due to reinfection. Immunity after effective treatment has been shown to be insufficient to prevent reinfection with HCV in individuals with ongoing risk of infection, including people who inject drugs (PWID), men having sex with men, and health care workers with frequent exposure to blood and bodily fluids.3Midgard H. Bjoro B. Maeland A. et al.Hepatitis C reinfection after sustained virological response.J Hepatol. 2016; 64: 1020-1026Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 4Martin T.C. Martin N.K. Hickman M. et al.Hepatitis C virus reinfection incidence and treatment outcome among HIV-positive MSM.AIDS. 2013; 27: 2551-2557Crossref PubMed Scopus (95) Google Scholar, 5Pineda J.A. Nunez-Torres R. Tellez F. et al.Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C.J Infect. 2015; 71: 571-577Abstract Full Text Full Text PDF PubMed Google Scholar, 6Martinello M. Grebely J. Petoumenos K. et al.HCV reinfection incidence among individuals treated for recent infection.J Viral Hepat. 2017; 24: 359-370Crossref PubMed Scopus (10) Google Scholar Rates of reinfection in these populations vary, but are high when those most at risk of transmitting infection are treated, in part as a means to interrupt transmission. A recent study in PWID treated while actively injecting showed 6-month and 18-month reinfection rates of 12.6 and 17.1 per 100 person-years, respectively.7Schulkind J. Ahmad F. Stephens B. et al.EASL International Liver Conference, Paris France. 2018. Abstract THU-063 Eradicate hepatitis C: a pilot of treatment as prevention in active drug users.J Hepatol. 2018; 68Google Scholar PWID, men who have sex with men, health care workers, infants born to HCV-infected mothers, and those living in the many countries with high HCV incidence would be expected to benefit from a preventive HCV vaccine. The effects of prophylactic vaccines with varying levels of efficacy and delivery strategies have been modeled.8Hahn J.A. Wylie D. Dill J. et al.Potential impact of vaccination on the hepatitis C virus epidemic in injection drug users.Epidemics. 2009; 1: 47-57Crossref PubMed Scopus (0) Google Scholar, 9Scott N. McBryde E. Vickerman P. et al.The role of a hepatitis C virus vaccine: modelling the benefits alongside direct-acting antiviral treatments.BMC Med. 2015; 13: 198Crossref PubMed Scopus (18) Google Scholar, 10Stone J. Martin N.K. Hickman M. et al.The potential impact of a hepatitis C vaccine for people who inject drugs: is a vaccine needed in the age of direct-acting antivirals?.PLoS One. 2016; 11: e0156213Crossref PubMed Scopus (13) Google Scholar Based on these models, high vaccination rates of high-risk seronegative PWID, even with a vaccine with only 30% efficacy, would have significant effects on transmission. Global control will require annual rates of cure that are consistently and significantly higher than new HCV infection rates. Few countries are on target to eliminate HCV as a public health problem by 2030, the goal set by the World Health Organization in 2016, and nearly 60% of surveyed countries had more infections than cures in 2016.11Hill A.M. Nath S. Simmons B. The road to elimination of hepatitis C: analysis of cures versus new infections in 91 countries.J Virus Erad. 2017; 3: 117-123Crossref PubMed Google Scholar, 12World Health OrganizationGlobal Hepatitis Report 2017.http://apps.who.int/iris/bitstream/handle/10665/255016/9789241565455-eng.pdf?sequence=1Google Scholar Consequently, control is unlikely to occur without improved focus on and success in reducing the number of new HCV infections in addition to cure. An effective preventive vaccine would have a significant effects on HCV incidence and would provide a major advance toward global HCV control. However, there are barriers to development, including limitations to HCV culture systems, virus diversity, limited models, and at-risk populations for testing vaccines, and incomplete understanding of protective immune responses. Generation of live-attenuated and inactivated whole virus vaccines has been effective against other viruses, but neither strategy is feasible for generating HCV vaccines. The inability to culture HCV (until recently) and ongoing limitations of HCV culture systems have posed challenges to production of a live-attenuated or inactivated whole HCV vaccine.13Thomas E. Liang T.J. Experimental models of hepatitis B and C—new insights and progress.Nat Rev Gastroenterol Hepatol. 2016; 13: 362-374Crossref PubMed Scopus (20) Google Scholar Culture strains of HCV have adaptive mutations that increase replication efficiency in vitro with unknown effects on replication in humans. Live-attenuated vaccines against other viruses have been generated in 2 primary ways: by passage of virus in nonhuman primate cell lines in which natural variants can arise; these have reduced replication in human cells, and by genetic deletion or inactivation of virulence factors. However, HCV does not replicate at high levels in nonhuman primate cell lines and virulence factors for HCV have not been defined. Practical production aspects and the risk of causing HCV infection with live-attenuated vaccines limit their utility. A principal challenge for HCV vaccine development is the extraordinary genetic diversity of the virus. With 7 known genotypes and more than 80 subtypes, the genetic diversity of HCV exceeds that of human immunodeficiency virus-1 (Figure 1). HCV strains from different genotypes differ, on average, at approximately 30% of their amino acids, whereas different subtypes within each genotype differ at an average of approximately 15% of their amino acids.14Smith D.B. Bukh J. Kuiken C. et al.Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource.Hepatology. 2014; 59: 318-327Crossref PubMed Scopus (648) Google Scholar, 15Bukh J. The history of hepatitis C virus (HCV): basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control.J Hepatol. 2016; 65: S2-S21Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 16Smith D.B. Meyers G. Bukh J. et al.Proposed revision to the taxonomy of the genus Pestivirus, family Flaviviridae.J Gen Virol. 2017; 98: 2106-2112Crossref PubMed Scopus (17) Google Scholar In addition to diversity among genotypes and subtypes, immune selection and the error-prone polymerase of the virus generate a diverse quasispecies of related but genetically distinct viral variants within each infected individual, presenting many opportunities for selection of viral variants with resistance to T-cell and antibody responses.17Martell M. Esteban J.I. Quer J. et al.Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution.J Virol. 1992; 66: 3225-3229Crossref PubMed Google Scholar, 18Farci P. Bukh J. Purcell R.H. The quasispecies of hepatitis C virus and the host immune response.Springer Semin Immunopathol. 1997; 19: 5-26Crossref PubMed Scopus (0) Google Scholar, 19Forns X. Purcell R.H. Bukh J. Quasispecies in viral persistence and pathogenesis of hepatitis C virus.Trends Microbiol. 1999; 7: 402-410Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 20Cox A.L. Mosbruger T. Mao Q. et al.Cellular immune selection with hepatitis C virus persistence in humans.J Exp Med. 2005; 201: 1741-1752Crossref PubMed Scopus (227) Google Scholar, 21Erickson A.L. Houghton M. Choo Q.L. et al.Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.J Immunol. 1993; 151: 4189-4199PubMed Google Scholar, 22Liu L. Fisher B.E. Dowd K.A. et al.Acceleration of hepatitis C virus envelope evolution in humans is consistent with progressive humoral immune selection during the transition from acute to chronic infection.J Virol. 2010; 84: 5067-5077Crossref PubMed Scopus (0) Google Scholar, 23Timm J. Lauer G.M. Kavanagh D.G. et al.CD8 epitope escape and reversion in acute HCV infection.J Exp Med. 2004; 200: 1593-1604Crossref PubMed Scopus (229) Google Scholar Several recent studies have demonstrated that antibody resistance can arise from mutations either within or distant from antibody binding epitopes, providing the virus with additional mechanisms of immune escape.24Bailey J.R. Wasilewski L.N. Snider A.E. et al.Naturally selected hepatitis C virus polymorphisms confer broad neutralizing antibody resistance.J Clin Invest. 2015; 125: 437-447Crossref PubMed Scopus (34) Google Scholar, 25Carlsen T.H. Pedersen J. Prentoe J.C. et al.Breadth of neutralization and synergy of clinically relevant human monoclonal antibodies against HCV genotypes 1a, 1b, 2a, 2b, 2c, and 3a.Hepatology. 2014; 60: 1551-1562Crossref PubMed Scopus (33) Google Scholar, 26El-Diwany R. Cohen V.J. Mankowski M.C. et al.Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.PLoS Pathog. 2017; 13: e1006235Crossref PubMed Scopus (7) Google Scholar Given this viral diversity within and between infected individuals, vaccine induction of very broadly reactive immune responses or the generation of immune responses that target genetically conserved regions of the viral genome may be required for protection against HCV infection or persistence. Another barrier to HCV vaccine development is the lack of in vitro systems and immunocompetent small animal models that facilitate determining whether vaccination induces protective immunity.13Thomas E. Liang T.J. Experimental models of hepatitis B and C—new insights and progress.Nat Rev Gastroenterol Hepatol. 2016; 13: 362-374Crossref PubMed Scopus (20) Google Scholar The discovery of an HCV-like virus, the rat Hepacivirus, will generate a new small animal model for vaccine testing. The limitation of this model is that although this virus is structurally analogous to HCV, it has limited sequence homology with HCV.27Billerbeck E. Wolfisberg R. Fahnoe U. et al.Mouse models of acute and chronic hepacivirus infection.Science. 2017; 357: 204-208Crossref PubMed Scopus (24) Google Scholar, 28Trivedi S. Murthy S. Sharma H. et al.Viral persistence, liver disease and host response in Hepatitis C-like virus rat model.Hepatology. 2017; 68: 435-448Crossref Scopus (5) Google Scholar Although the success of DAA therapy has resulted in discussions of HCV challenge studies, in which vaccinated subjects would be intentionally infected with HCV, it is not clear how those infections would be achieved. Primary HCV isolates have limited ability to replicate in tissue culture, restricting their production. In addition, primary HCV isolates are not expressed in good manufacturing process-compliant cell lines and do not represent the viral diversity of the quasispecies circulating in natural infection. Direct infusion of HCV-infected human plasma might be considered, but would require careful screening for other pathogens and, even with thoughtful selection of inoculum levels and HCV genotypes, might fail to completely recapitulate natural exposure. An effective vaccine is therefore difficult to validate unless it is tested in populations with a predictably high risk for HCV infection. Although HCV transmission occurs through blood transfusion and invasive medical procedures, identifying people who could be at risk of transmission via those routes and vaccinating them before exposure is not feasible. PWID are at predictably high risk with the incidence of HCV infection (ranging from 5% to 25% per year), so they could be a suitable test population for HCV vaccines, and there is a continued need for prevention of HCV infection in this population.29Cox A.L. Thomas D.L. Hepatitis C virus vaccines among people who inject drugs.Clin Infect Dis. 2013; 57: S46-S50Crossref PubMed Scopus (25) Google Scholar However, few studies have successfully managed the identification, enrollment, and prospective monitoring of PWID before onset of acute HCV infection.30Cox A.L. Page K. Bruneau J. et al.Rare birds in North America: acute hepatitis C cohorts.Gastroenterology. 2009; 136: 26-31Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 31Edlin B.R. Shu M.A. Winkelstein E. et al.More rare birds, and the occasional swan.Gastroenterology. 2009; 136: 2412-2414Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar These cohorts will likely remain of critical importance to vaccine testing and help us increase our understanding of the host responses required for protective immunity. Knowing what immune responses indicate protective immunity would permit testing of candidate vaccines in healthy adults not at risk for infection first. With correlates of protection known, only those vaccines that elicit effective immune responses would advance to testing in at-risk populations for verification of protection, permitting judicious use of these PWID cohorts. Although our incomplete understanding of protective immunity against HCV is a barrier to vaccine development, studies have provided substantial evidence that protective immunity does exist. Spontaneous clearance of HCV infection occurs in approximately 25% of acutely infected individuals.32Micallef J.M. Kaldor J.M. Dore G.J. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies.J Viral Hepat. 2006; 13: 34-41Crossref PubMed Scopus (522) Google Scholar Chimpanzees and humans who spontaneously control an initial HCV infection can develop recurrent HCV viremia following additional HCV exposure, so spontaneous clearance of primary HCV infection does not generate sterilizing immunity.33Farci P. Alter H.J. Govindarajan S. et al.Lack of protective immunity against reinfection with hepatitis C virus.Science. 1992; 258: 135-140Crossref PubMed Google Scholar, 34Prince A.M. Immunity in hepatitis C virus infection.Vox Sang. 1994; 67: 227-228PubMed Google Scholar, 35Bassett S.E. Guerra B. Brasky K. et al.Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection.Hepatology. 2001; 33: 1479-1487Crossref PubMed Scopus (190) Google Scholar, 36Major M.E. Mihalik K. Puig M. et al.Previously infected and recovered chimpanzees exhibit rapid responses that control hepatitis C virus replication upon rechallenge.J Virol. 2002; 76: 6586-6595Crossref PubMed Scopus (0) Google Scholar, 37Nascimbeni M. Mizukoshi E. Bosmann M. et al.Kinetics of CD4+ and CD8+ memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees.J Virol. 2003; 77: 4781-4793Crossref PubMed Scopus (0) Google Scholar, 38Shoukry N.H. Grakoui A. Houghton M. et al.Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection.J Exp Med. 2003; 197: 1645-1655Crossref PubMed Scopus (446) Google Scholar, 39Mehta S.H. Cox A. Hoover D.R. et al.Protection against persistence of hepatitis C.Lancet. 2002; 359: 1478-1483Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar, 40Osburn W.O. Fisher B.E. Dowd K.A. et al.Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.Gastroenterology. 2010; 138: 315-324Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar, 41Prince A.M. Brotman B. Lee D.H. et al.Protection against chronic hepatitis C virus infection after rechallenge with homologous, but not heterologous, genotypes in a chimpanzee model.J Infect Dis. 2005; 192: 1701-1709Crossref PubMed Scopus (0) Google Scholar, 42Micallef J.M. Macdonald V. Jauncey M. et al.High incidence of hepatitis C virus reinfection within a cohort of injecting drug users.J Viral Hepat. 2007; 14: 413-418Crossref PubMed Scopus (87) Google Scholar, 43van de Laar T.J. Molenkamp R. van den Berg C. et al.Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam.J Hepatol. 2009; 51: 667-674Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 44Page K. Hahn J.A. Evans J. et al.Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection.J Infect Dis. 2009; 200: 1216-1226Crossref PubMed Scopus (190) Google Scholar The discovery that spontaneous immunologic control of HCV does not always result in protective immunity initially decreased confidence that prophylactic vaccination was possible. However, clearance of multiple infections with homologous and heterologous virus has been observed in chimpanzees and humans.35Bassett S.E. Guerra B. Brasky K. et al.Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection.Hepatology. 2001; 33: 1479-1487Crossref PubMed Scopus (190) Google Scholar, 40Osburn W.O. Fisher B.E. Dowd K.A. et al.Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.Gastroenterology. 2010; 138: 315-324Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar, 41Prince A.M. Brotman B. Lee D.H. et al.Protection against chronic hepatitis C virus infection after rechallenge with homologous, but not heterologous, genotypes in a chimpanzee model.J Infect Dis. 2005; 192: 1701-1709Crossref PubMed Scopus (0) Google Scholar, 42Micallef J.M. Macdonald V. Jauncey M. et al.High incidence of hepatitis C virus reinfection within a cohort of injecting drug users.J Viral Hepat. 2007; 14: 413-418Crossref PubMed Scopus (87) Google Scholar, 44Page K. Hahn J.A. Evans J. et al.Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection.J Infect Dis. 2009; 200: 1216-1226Crossref PubMed Scopus (190) Google Scholar, 45Grebely J. Prins M. Hellard M. et al.Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine.Lancet Infect Dis. 2012; 12: 408-414Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar Furthermore, reinfections are cleared more often than primary infections. Reinfected PWID control secondary HCV infections approximately 80% of the time, essentially the reverse of rates of clearance vs persistence observed in primary infection.40Osburn W.O. Fisher B.E. Dowd K.A. et al.Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.Gastroenterology. 2010; 138: 315-324Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar Although genetic traits and other unmodifiable traits affect overall clearance rates, they would not alter the pace of clearance in reinfection. In contrast, adaptive immune responses would be expected to result in more rapid control of reinfection than occurs in the initial infection. Supporting the hypothesis that adaptive immunity induced in control of a primary infection leads to more effective clearance of subsequent infections, Lanford et al46Lanford R.E. Guerra B. Chavez D. et al.Cross-genotype immunity to hepatitis C virus.J Virol. 2004; 78: 1575-1581Crossref PubMed Scopus (143) Google Scholar reported decreased duration and magnitude of viremia in chimpanzees in reinfection vs primary infection, regardless of whether the chimpanzees were infected with homologous or heterologous viruses. HCV reinfection in humans is also characterized by a reduced peak and duration of viremia compared with initial infection of the same person.40Osburn W.O. Fisher B.E. Dowd K.A. et al.Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.Gastroenterology. 2010; 138: 315-324Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar, 47Sacks-Davis R. Grebely J. Dore G.J. et al.Hepatitis C virus reinfection and spontaneous clearance of reinfection—the InC3 Study.J Infect Dis. 2015; 212: 1407-1419Crossref PubMed Scopus (32) Google Scholar Reinfection was associated with broadened cellular immune responses compared with primary infection and the presence of broadly cross-reactive neutralizing antibodies (NAbs).40Osburn W.O. Fisher B.E. Dowd K.A. et al.Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.Gastroenterology. 2010; 138: 315-324Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar The more rapid and effective control of viral replication with subsequent exposures, compared with the initial exposure, indicates that adaptive immunity is induced and, although not sterilizing, protects against chronic infection. Additional research on effective immune control of HCV is needed to develop a vaccine, including studies of people with repeated spontaneous control of diverse HCV infections over time. Decades of research have revealed that HCV-specific CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies all play a role in protection against persistent HCV infection. Vaccine strategies to induce all 3 adaptive immune responses are in development. Data from human and chimpanzee studies have indicated that HCV-specific CD4+ and CD8+ T cells are crucial in control of primary and secondary HCV infections. There is indirect evidence for T-cell control from genetic studies, which demonstrated an association between HCV clearance and specific class-I and class-II HLAs, which present HCV peptides to CD8+ and CD4+ T cells, respectively.48Kuniholm M.H. Kovacs A. Gao X. et al.Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia.Hepatology. 2010; 51: 1514-1522Crossref PubMed Scopus (69) Google Scholar, 49Duggal P. Thio C.L. Wojcik G.L. et al.Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.Ann Intern Med. 2013; 158: 235-245Crossref PubMed Scopus (123) Google Scholar A vigorous and multispecific proliferative CD4+ T-cell response against HCV proteins has been correlated with spontaneous control of acute HCV infection.50Schulze zur Wiesch J. Ciuffreda D. Lewis-Ximenez L. et al.Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence.J Exp Med. 2012; 209: 61-75Crossref PubMed Scopus (112) Google Scholar, 51Diepolder H.M. Zachoval R. Hoffmann R.M. et al.The role of hepatitis C virus specific CD4+ T lymphocytes in acute and chronic hepatitis C.J Mol Med (Berl). 1996; 74: 583-588Crossref PubMed Scopus (96) Google Scholar, 52Chang K.M. Thimme R. Melpolder J.J. et al.Differential CD4(+) and CD8(+) T-cell responsiveness in hepatitis C virus infection.Hepatology. 2001; 33: 267-276Crossref PubMed Scopus (295) Google Scholar, 53Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence.J Clin Invest. 2009; 119: 1745-1754Crossref PubMed Scopus (392) Google Scholar Schulze zur Wiesch et al50Schulze zur Wiesch J. Ciuffreda D. Lewis-Ximenez L. et al.Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence.J Exp Med. 2012; 209: 61-75Crossref PubMed Scopus (112) Google Scholar demonstrated that broadly directed HCV-specific CD4+ T cells are detectable during early stages of infection, regardless of outcome. However, CD4+ T cells have functional defects during early stages of chronic HCV infection, and rapidly become undetectable with progression, whereas CD4+ T cells are more often maintained with virus clearance. The ineffective CD4+ T cells are thought to impair the response of CD8+ T cells, and are associated with persistent infection, T-cell exhaustion, and selection of HCV variants with escape mutations in class I epitopes.53Rehermann B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence.J Clin Invest. 2009; 119: 1745-1754Crossref PubMed Scopus (392) Google Scholar Generation of an effective memory response is required for successful vaccination. Reinfection studies provide evidence for the important role of T-cell memory in HCV control. Antibody-mediated depletion of CD4+ T cells before reinfection of 2 immune chimpanzees resulted in persistence of HCV despite functional intrahepatic memory CD8+ T-cell responses.54Grakoui A. Shoukry N.H. Woollard D.J. et al.HCV persistence and immune evasion in the absence of memory T cell help.Science. 2003; 302: 659-662Crossref PubMed Scopus (611) Google Scholar Antibody-mediated depletion of CD8+ T cells immediately before the third infection of 2 chimpanzees that had previously cleared infection resulted in prolonged viremia, which was controlled only when CD8+ T cells were again detectable in the liver.38Shoukry N.H. Grakoui A. Houghton M. et al.Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection.J Exp Med. 2003; 197: 1645-1655Crossref PubMed Scopus (446) Google Scholar Similarly, protection against viral persistence in recurrent HCV infection in PWID was associated w" @default.
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• W2894067555 title "Approaches, Progress, and Challenges to Hepatitis C Vaccine Development" @default.
• W2894067555 cites W1569603086 @default.
• W2894067555 cites W1600254581 @default.
• W2894067555 cites W1656291587 @default.
• W2894067555 cites W1762830534 @default.
• W2894067555 cites W1847394961 @default.
• W2894067555 cites W1890688926 @default.
• W2894067555 cites W1902746983 @default.
• W2894067555 cites W1952863055 @default.
• W2894067555 cites W1953340689 @default.
• W2894067555 cites W1956205882 @default.
• W2894067555 cites W1963617829 @default.
• W2894067555 cites W1963707175 @default.
• W2894067555 cites W1964573817 @default.
• W2894067555 cites W1967491261 @default.
• W2894067555 cites W1970880058 @default.
• W2894067555 cites W1974789298 @default.
• W2894067555 cites W1978916431 @default.
• W2894067555 cites W1981136135 @default.
• W2894067555 cites W1982514203 @default.
• W2894067555 cites W1983233990 @default.
• W2894067555 cites W1985982900 @default.
• W2894067555 cites W1987173750 @default.
• W2894067555 cites W1992465744 @default.
• W2894067555 cites W1993023565 @default.
• W2894067555 cites W1993075096 @default.
• W2894067555 cites W1996295206 @default.
• W2894067555 cites W1998427156 @default.
• W2894067555 cites W1998738356 @default.
• W2894067555 cites W2000782434 @default.
• W2894067555 cites W2000827554 @default.
• W2894067555 cites W2000835793 @default.
• W2894067555 cites W2004651002 @default.
• W2894067555 cites W2008860633 @default.
• W2894067555 cites W2013534419 @default.
• W2894067555 cites W2014690236 @default.
• W2894067555 cites W2014920221 @default.
• W2894067555 cites W2017359325 @default.
• W2894067555 cites W2017775841 @default.
• W2894067555 cites W2021117977 @default.
• W2894067555 cites W2022077416 @default.
• W2894067555 cites W2028757382 @default.
• W2894067555 cites W2030329053 @default.
• W2894067555 cites W2031615680 @default.
• W2894067555 cites W2035848056 @default.
• W2894067555 cites W2036791296 @default.
• W2894067555 cites W2036836249 @default.
• W2894067555 cites W2037494007 @default.
• W2894067555 cites W2038281342 @default.
• W2894067555 cites W2045436136 @default.
• W2894067555 cites W2046182783 @default.
• W2894067555 cites W2047619471 @default.
• W2894067555 cites W2050671757 @default.
• W2894067555 cites W2053263959 @default.
• W2894067555 cites W2053536599 @default.
• W2894067555 cites W2054802322 @default.
• W2894067555 cites W2058115636 @default.
• W2894067555 cites W2062676055 @default.
• W2894067555 cites W2064778609 @default.
• W2894067555 cites W2064807794 @default.
• W2894067555 cites W2066890172 @default.
• W2894067555 cites W2069910822 @default.
• W2894067555 cites W2071928914 @default.
• W2894067555 cites W2072731749 @default.
• W2894067555 cites W2072859701 @default.
• W2894067555 cites W2084265216 @default.
• W2894067555 cites W2085716095 @default.
• W2894067555 cites W2086853864 @default.
• W2894067555 cites W2089638478 @default.
• W2894067555 cites W2089866845 @default.
• W2894067555 cites W2090297731 @default.
• W2894067555 cites W2094254049 @default.
• W2894067555 cites W2095641332 @default.
• W2894067555 cites W2096347191 @default.
• W2894067555 cites W2098188322 @default.
• W2894067555 cites W2100260641 @default.
• W2894067555 cites W2101285175 @default.
• W2894067555 cites W2102253058 @default.
• W2894067555 cites W2103802132 @default.
• W2894067555 cites W2105249005 @default.
• W2894067555 cites W2107530112 @default.
• W2894067555 cites W2107629382 @default.
• W2894067555 cites W2108362208 @default.
• W2894067555 cites W2109464107 @default.
• W2894067555 cites W2109514681 @default.
• W2894067555 cites W2109954381 @default.
• W2894067555 cites W2110842901 @default.
• W2894067555 cites W2112274488 @default.
• W2894067555 cites W2113326602 @default.
• W2894067555 cites W2114215267 @default.
• W2894067555 cites W2122043154 @default.

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