The past, present and future of neutralizing antibodies for hepatitis C virus

Highlights • Recent studies have provided insight into the protective role of neutralizing antibodies in hepatitis C.• Neutralizing antibodies show broad reactivity for diverse HCV genotypes.• Recombinant HCV glycoproteins can elicit neutralizing antibodies.• The HCV E2 core structure can inform rational design of immunogens.

[1]  E. Blanchard,et al.  Hepatitis C Virus Entry Depends on Clathrin-Mediated Endocytosis , 2006, Journal of Virology.

[2]  B. Manicassamy,et al.  Dissecting the role of putative CD81 binding regions of E2 in mediating HCV entry: Putative CD81 binding region 1 is not involved in CD81 binding , 2008, Virology Journal.

[3]  B. Bartosch,et al.  Analysis of a Highly Flexible Conformational Immunogenic Domain A in Hepatitis C Virus E2 , 2005, Journal of Virology.

[4]  Pham Phung,et al.  Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target , 2009, Science.

[5]  S. Levy,et al.  Functional Analysis of Cell Surface-Expressed Hepatitis C Virus E2 Glycoprotein , 1999, Journal of Virology.

[6]  Stanley M. Lemon,et al.  Neutralizing Monoclonal Antibodies against Hepatitis C Virus E2 Protein Bind Discontinuous Epitopes and Inhibit Infection at a Postattachment Step , 2011, Journal of Virology.

[7]  Giorgio,et al.  Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Meola,et al.  An alpaca nanobody inhibits hepatitis C virus entry and cell‐to‐cell transmission , 2013, Hepatology.

[9]  C. Cheng‐Mayer,et al.  Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Bukh,et al.  Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate , 2012, PLoS pathogens.

[11]  Garrett M. Morris,et al.  Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design , 2001, Science.

[12]  T. Liang,et al.  Hepatitis C virus–like particles induce virus‐specific humoral and cellular immune responses in mice , 2001, Hepatology.

[13]  N. Kato,et al.  Genetic drift in hypervariable region 1 of the viral genome in persistent hepatitis C virus infection , 1994, Journal of virology.

[14]  P. Simmonds,et al.  Genetic diversity and evolution of hepatitis C virus--15 years on. , 2004, The Journal of general virology.

[15]  J. Dubuisson,et al.  Characterization of Hepatitis C Virus E2 Glycoprotein Interaction with a Putative Cellular Receptor, CD81 , 1999, Journal of Virology.

[16]  N. Kato,et al.  Humoral immune response to hypervariable region 1 of the putative envelope glycoprotein (gp70) of hepatitis C virus , 1993, Journal of virology.

[17]  W. Quint,et al.  Sequence analysis of hepatitis C virus genotypes 1 to 5 reveals multiple novel subtypes in the Benelux countries. , 1995, The Journal of general virology.

[18]  O. Weiland,et al.  Limited humoral immunity in hepatitis C virus infection. , 1999, Gastroenterology.

[19]  S. Emerson,et al.  In vitro assay for neutralizing antibody to hepatitis C virus: Evidence for broadly conserved neutralization epitopes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Zongyi Hu,et al.  Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees , 2007, Proceedings of the National Academy of Sciences.

[21]  A. Shavinskaya,et al.  Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[22]  John R. Mascola,et al.  Analysis of Neutralization Specificities in Polyclonal Sera Derived from Human Immunodeficiency Virus Type 1-Infected Individuals , 2008, Journal of Virology.

[23]  Robyn L Stanfield,et al.  Contrasting IgG structures reveal extreme asymmetry and flexibility. , 2002, Journal of molecular biology.

[24]  J. Bukh,et al.  Hypervariable Region 1 Differentially Impacts Viability of Hepatitis C Virus Strains of Genotypes 1 to 6 and Impairs Virus Neutralization , 2010, Journal of Virology.

[25]  Shelley L. Hemsley,et al.  Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection. , 2005, The Journal of general virology.

[26]  B. Rehermann.  Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells , 2013, Nature Medicine.

[27]  J. D. Capra,et al.  Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen , 2009, Nature Protocols.

[28]  D. Burton,et al.  Fc receptor but not complement binding is important in antibody protection against HIV , 2007, Nature.

[29]  A. Meola,et al.  Structural Basis of HCV Neutralization by Human Monoclonal Antibodies Resistant to Viral Neutralization Escape , 2013, PLoS pathogens.

[30]  C. Rice,et al.  CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells , 2009, The Journal of general virology.

[31]  D. Burton,et al.  An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. , 2012, Vaccine.

[32]  E. Robinet,et al.  Hepatitis C virus infection and related liver disease: the quest for the best animal model , 2013, Front. Microbiol..

[33]  M. Shapiro,et al.  Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  C. Rice,et al.  Characterization of Infectious Retroviral Pseudotype Particles Bearing Hepatitis C Virus Glycoproteins , 2004, Journal of Virology.

[35]  Toshiaki Maruyama,et al.  Complete Replication of Hepatitis C Virus in Cell Culture , 2005, Science.

[36]  R. Purcell,et al.  In vivo evaluation of the cross‐genotype neutralizing activity of polyclonal antibodies against hepatitis C virus , 2011, Hepatology.

[37]  Dennis R. Burton,et al.  Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design , 2003, Journal of Virology.

[38]  H. Hsu,et al.  Decreased diversity of hepatitis C virus quasispecies during bone marrow transplantation , 1999, Journal of medical virology.

[39]  Mario Roederer,et al.  Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 , 2010, Science.

[40]  P. Roingeard,et al.  Role of N-Linked Glycans in the Functions of Hepatitis C Virus Envelope Proteins Incorporated into Infectious Virions , 2010, Journal of Virology.

[41]  R. Clayton,et al.  Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2. , 2001, The Journal of general virology.

[42]  Nathan M. Sherer,et al.  Virus Cell-to-Cell Transmission , 2010, Journal of Virology.

[43]  R. Purcell,et al.  Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver–chimeric mice from infection with a homologous hepatitis C virus strain , 2008, Hepatology.

[44]  K. Ishii,et al.  Neutralizing antibodies induced by cell culture-derived hepatitis C virus protect against infection in mice. , 2013, Gastroenterology.

[45]  D. Lavillette,et al.  Monoclonal Antibody AP33 Defines a Broadly Neutralizing Epitope on the Hepatitis C Virus E2 Envelope Glycoprotein , 2005, Journal of Virology.

[46]  Richard T. Wyatt,et al.  Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals , 2009, Nature.

[47]  Hongying Duan,et al.  Amino Acid Residue-Specific Neutralization and Nonneutralization of Hepatitis C Virus by Monoclonal Antibodies to the E2 Protein , 2012, Journal of Virology.

[48]  K. Meyer,et al.  Complement-Mediated Enhancement of Antibody Function for Neutralization of Pseudotype Virus Containing Hepatitis C Virus E2 Chimeric Glycoprotein , 2002, Journal of Virology.

[49]  M. Ait-goughoulte,et al.  Antibody-Dependent Enhancement of Hepatitis C Virus Infection , 2007, Journal of Virology.

[50]  S. Emerson,et al.  Isolation and Characterization of Broadly Neutralizing Human Monoclonal Antibodies to the E1 Glycoprotein of Hepatitis C Virus , 2007, Journal of Virology.

[51]  M. Houghton,et al.  Immunization of human volunteers with hepatitis C virus envelope glycoproteins elicits antibodies that cross-neutralize heterologous virus strains. , 2011, The Journal of infectious diseases.

[52]  Stuart C. Ray,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 , 2010, Journal of Virology.

[53]  D. Lavillette,et al.  Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee , 2005, Hepatology.

[54]  E. Falkowska,et al.  Hepatitis C Virus Envelope Glycoprotein E2 Glycans Modulate Entry, CD81 Binding, and Neutralization , 2007, Journal of Virology.

[55]  D. Gatherer,et al.  Mutations within a Conserved Region of the Hepatitis C Virus E2 Glycoprotein That Influence Virus-Receptor Interactions and Sensitivity to Neutralizing Antibodies , 2010, Journal of Virology.

[56]  Arvind H. Patel,et al.  Analysis of Antigenicity and Topology of E2 Glycoprotein Present on Recombinant Hepatitis C Virus-Like Particles , 2002, Journal of Virology.

[57]  Hongying Duan,et al.  Structural evidence for a bifurcated mode of action in the antibody-mediated neutralization of hepatitis C virus , 2013, Proceedings of the National Academy of Sciences.

[58]  N. Chalasani,et al.  CD59 incorporation protects hepatitis C virus against complement‐mediated destruction , 2012, Hepatology.

[59]  C. Rice,et al.  Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies. , 2007, Vaccine.

[60]  A. Weiner,et al.  Vaccination of chimpanzees against infection by the hepatitis C virus. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[61]  M. Major,et al.  Immunization of chimpanzees with an envelope protein-based vaccine enhances specific humoral and cellular immune responses that delay hepatitis C virus infection. , 2004, Vaccine.

[62]  Jamie K. Scott,et al.  Molecular Features of the Broadly Neutralizing Immunoglobulin G1 b12 Required for Recognition of Human Immunodeficiency Virus Type 1 gp120 , 2003, Journal of Virology.

[63]  Michel C Nussenzweig,et al.  Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. , 2008, Journal of immunological methods.

[64]  T. Liang,et al.  Hepatitis C virus–like particles combined with novel adjuvant systems enhance virus‐specific immune responses , 2003, Hepatology.

[65]  K. Meyer,et al.  Transcriptional Repression of C4 Complement by Hepatitis C Virus Proteins , 2011, Journal of Virology.

[66]  M. Houghton,et al.  A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein , 2008, The Journal of general virology.

[68]  C. Rice,et al.  Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. , 2007, Gastroenterology.

[69]  A. Tarr,et al.  Identification of a Broadly Cross-Reacting and Neutralizing Human Monoclonal Antibody Directed against the Hepatitis C Virus E2 Protein , 2007, Journal of Virology.

[70]  A. Zibert,et al.  Early antibody response against hypervariable region 1 is associated with acute self‐limiting infections of hepatitis C virus , 1997, Hepatology.

[71]  S. Jacobson,et al.  Patients infected with the same hepatitis C virus strain display different kinetics of the isolate-specific antibody response. , 1997, The Journal of infectious diseases.

[72]  H J Alter,et al.  The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. , 2000, Science.

[73]  S. Ray,et al.  Selection pressure from neutralizing antibodies drives sequence evolution during acute infection with hepatitis C virus. , 2009, Gastroenterology.

[74]  A. Tarr,et al.  Naturally Occurring Antibodies That Recognize Linear Epitopes in the Amino Terminus of the Hepatitis C Virus E2 Protein Confer Noninterfering, Additive Neutralization , 2011, Journal of Virology.

[75]  G. Taylor,et al.  Toward a Hepatitis C Virus Vaccine: the Structural Basis of Hepatitis C Virus Neutralization by AP33, a Broadly Neutralizing Antibody , 2012, Journal of Virology.

[76]  D. Burton,et al.  Robust hepatitis C virus infection in vitro. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[77]  D. Samuel,et al.  Incidence of Hepatitis C in Patients Receiving Different Preparations of Hepatitis B Immunoglobulins after Liver Transplantation , 1998, Annals of Internal Medicine.

[78]  I. Jacobson,et al.  Emerging therapeutic targets for hepatitis C virus infection. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[79]  P. Mangeot,et al.  A Prime-Boost Strategy Using Virus-Like Particles Pseudotyped for HCV Proteins Triggers Broadly Neutralizing Antibodies in Macaques , 2011, Science Translational Medicine.

[80]  D. Tyrrell,et al.  Hepatitis C virus replication in mice with chimeric human livers , 2001, Nature Medicine.

[81]  Cynthia L. de la Fuente,et al.  Animal models for hepatitis C. , 2013, Current topics in microbiology and immunology.

[82]  Jin Zhong,et al.  Identification of a Residue in Hepatitis C Virus E2 Glycoprotein That Determines Scavenger Receptor BI and CD81 Receptor Dependency and Sensitivity to Neutralizing Antibodies , 2008, Journal of Virology.

[83]  Boguslaw Stec,et al.  Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses , 2009, Nature Structural &Molecular Biology.

[84]  D. Burton.  Antibodies, viruses and vaccines , 2002, Nature Reviews Immunology.

[85]  A. Tarr,et al.  Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus , 2007, Proceedings of the National Academy of Sciences.

[86]  C. G. Wu,et al.  Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma , 2007, Proceedings of the National Academy of Sciences.

[87]  Zongyi Hu,et al.  Immunization with Hepatitis C Virus-Like Particles Induces Humoral and Cellular Immune Responses in Nonhuman Primates , 2004, Journal of Virology.

[88]  E. Galun,et al.  Preclinical Evaluation of Two Neutralizing Human Monoclonal Antibodies against Hepatitis C Virus (HCV): a Potential Treatment To Prevent HCV Reinfection in Liver Transplant Patients , 2006, Journal of Virology.

[89]  Brian Clegg,et al.  The candidate , 2016, Commun. ACM.

[90]  J. Bukh,et al.  Development and characterization of hepatitis C virus genotype 1‐7 cell culture systems: Role of CD81 and scavenger receptor class B type I and effect of antiviral drugs , 2009, Hepatology.

[91]  M. Houghton,et al.  Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC). , 2005, Journal of hepatology.

[92]  Arvind H. Patel,et al.  Analysis of Antigenicity and Topology of E2 Glycoprotein Present on Recombinant Hepatitis C Virus-Like Particles , 2002, Journal of Virology.

[93]  Martin A. Nowak,et al.  Antibody neutralization and escape by HIV-1 , 2003, Nature.

[94]  D. Ennishi,et al.  Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV‐infected CD20‐positive B‐cell lymphoma undergoing rituximab combination chemotherapy , 2008, American journal of hematology.

[95]  J. Hoofnagle,et al.  Antibodies Against Hepatitis C Virus–Like Particles and Viral Clearance in Acute and Chronic Hepatitis C , 2000, Hepatology.

[96]  R. Purcell,et al.  Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[97]  Y. Muraki,et al.  Effect of the Addition of Oligosaccharides on the Biological Activities and Antigenicity of Influenza A/H3N2 Virus Hemagglutinin , 2004, Journal of Virology.

[98]  Heiyoung Park,et al.  Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion. , 2012, The Journal of infectious diseases.

[99]  S. Ray,et al.  Clearance of hepatitis C infection is associated with the early appearance of broad neutralizing antibody responses , 2014, Hepatology.

[100]  T. Liang,et al.  Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[101]  R. Purcell,et al.  The natural history of infection with hepatitis C virus (HCV) in chimpanzees: comparison of serologic responses measured with first- and second-generation assays and relationship to HCV viremia. , 1992, The Journal of infectious diseases.

[102]  I. Wilson,et al.  Structure of Hepatitis C Virus Envelope Glycoprotein E2 Antigenic Site 412 to 423 in Complex with Antibody AP33 , 2012, Journal of Virology.

[103]  M. Diamond,et al.  Hepatitis C Virus Infection Upregulates CD55 Expression on the Hepatocyte Surface and Promotes Association with Virus Particles , 2013, Journal of Virology.

[104]  M. Major,et al.  Depletion of interfering antibodies in chronic hepatitis C patients and vaccinated chimpanzees reveals broad cross-genotype neutralizing activity , 2009, Proceedings of the National Academy of Sciences.

[105]  O. Pybus,et al.  Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection , 2009, Journal of Virology.

[106]  R. Purcell,et al.  Neutralizing antibodies against hepatitis C virus and the emergence of neutralization escape mutant viruses , 1994, Journal of virology.

[107]  G. Davis,et al.  A randomized, open‐label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[108]  J. Bukh,et al.  Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies , 2013, Hepatology.

[109]  M. Lai,et al.  Establishment of B-Cell Lymphoma Cell Lines Persistently Infected with Hepatitis C Virus In Vivo and In Vitro: the Apoptotic Effects of Virus Infection , 2003, Journal of Virology.

[110]  A. Folgori,et al.  Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man , 2012, Science Translational Medicine.

[111]  J. McKeating,et al.  Hepatitis C virus cell‐cell transmission in hepatoma cells in the presence of neutralizing antibodies , 2007, Hepatology.

[112]  H. Van Vlierberghe,et al.  A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C , 2003, Hepatology.

[113]  R. Tafi,et al.  Mimotopes of the hepatitis C virus hypervariable region 1, but not the natural sequences, induce cross‐reactive antibody response by genetic immunization , 2001, Hepatology.

[114]  D. Wong,et al.  Hepatitis C Virus Structural Proteins Assemble into Viruslike Particles in Insect Cells , 1998, Journal of Virology.

[115]  B. Bartosch,et al.  Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes , 2003, The Journal of experimental medicine.

[116]  J. Dubuisson,et al.  Hepatitis C Virus (HCV)-Induced Immunoglobulin Hypermutation Reduces the Affinity and Neutralizing Activities of Antibodies against HCV Envelope Protein , 2008, Journal of Virology.

[117]  R. Purcell,et al.  Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees , 2012, PLoS pathogens.

[118]  R. Bartenschlager,et al.  Characterization of the hepatitis C virus E2 epitope defined by the broadly neutralizing monoclonal antibody AP33 , 2006, Hepatology.

[119]  Robyn L. Stanfield,et al.  Hepatitis C Virus E2 Envelope Glycoprotein Core Structure , 2013, Science.

[120]  A. Maerz,et al.  A Conserved Gly436-Trp-Leu-Ala-Gly-Leu-Phe-Tyr Motif in Hepatitis C Virus Glycoprotein E2 Is a Determinant of CD81 Binding and Viral Entry , 2006, Journal of Virology.

[121]  R. Bartenschlager,et al.  Production of infectious hepatitis C virus in tissue culture from a cloned viral genome , 2005, Nature Medicine.

[122]  C. Rice,et al.  Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses , 1994, Journal of virology.

[123]  Shailesh V. Date,et al.  Glycan shifting on hepatitis C virus (HCV) E2 glycoprotein is a mechanism for escape from broadly neutralizing antibodies. , 2013, Journal of molecular biology.

[124]  Paul W. H. I. Parren,et al.  Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120 , 2003, Journal of Virology.

[125]  P. Zamore,et al.  Human Monoclonal Antibody MBL‐HCV1 Delays HCV Viral Rebound Following Liver Transplantation: A Randomized Controlled Study , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[126]  D. Burton,et al.  Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge , 2008, Nature Medicine.

[127]  J. Skehel,et al.  A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins , 2011, Science.

[128]  T. Dragic,et al.  Hepatitis C Virus Entry Requires a Critical Postinternalization Step and Delivery to Early Endosomes via Clathrin-Coated Vesicles , 2006, Journal of Virology.

[129]  D. Burton,et al.  Immunofocusing: antigen engineering to promote the induction of HIV-neutralizing antibodies. , 2003, Trends in molecular medicine.

[130]  J. Bukh,et al.  Cooperativity in Virus Neutralization by Human Monoclonal Antibodies to Two Adjacent Regions Located at the Amino Terminus of Hepatitis C Virus E2 Glycoprotein , 2012, Journal of Virology.

[131]  M. Houghton,et al.  Intrahepatic Genetic Inoculation of Hepatitis C Virus RNA Confers Cross-Protective Immunity , 2001, Journal of Virology.

[132]  F. Penin,et al.  Additional glycosylation within a specific hypervariable region of subtype 3a of hepatitis C virus protects against virus neutralization. , 2013, The Journal of infectious diseases.

[133]  Thomas F. Baumert,et al.  Neutralizing Antibody-Resistant Hepatitis C Virus Cell-to-Cell Transmission , 2010, Journal of Virology.

[134]  K. Meyer,et al.  Hepatitis C Virus Proteins Inhibit C3 Complement Production , 2011, Journal of Virology.

[135]  C. Rice,et al.  Emerging therapies for the treatment of hepatitis C , 2013, EMBO molecular medicine.

[136]  F. Penin,et al.  The Neutralizing Activity of Anti-Hepatitis C Virus Antibodies Is Modulated by Specific Glycans on the E2 Envelope Protein , 2007, Journal of Virology.

[137]  J. Hoofnagle,et al.  Sequence analysis of hepatitis C virus from patients with relapse after a sustained virological response: relapse or reinfection? , 2014, The Journal of infectious diseases.

[138]  Birke Bartosch,et al.  Role of N-Linked Glycans in the Functions of Hepatitis C Virus Envelope Glycoproteins , 2005, Journal of Virology.

[139]  J. Sodroski,et al.  The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus , 2008, Nature Reviews Microbiology.

[140]  A Cerino,et al.  Hypervariable region 1 of hepatitis C virus: immunological decoy or biologically relevant domain? , 2001, Antiviral research.

[141]  D. Burton,et al.  Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1 , 2012, Proceedings of the National Academy of Sciences.

[142]  Charles M. Rice,et al.  Completion of the entire hepatitis C virus life-cycle in genetically humanized mice , 2013, Nature.

[143]  Mark Connors,et al.  Broad HIV-1 neutralization mediated by CD4-binding site antibodies , 2007, Nature Medicine.

[144]  D. Vlahov,et al.  Protection against persistence of hepatitis C , 2002, The Lancet.

[145]  S. Khalid,et al.  Specific Acquisition of Functional CD59 but Not CD46 or CD55 by Hepatitis C Virus , 2012, PloS one.

[146]  S. Lemon,et al.  Definition of a Conserved Immunodominant Domain on Hepatitis C Virus E2 Glycoprotein by Neutralizing Human Monoclonal Antibodies , 2008, Journal of Virology.

[147]  T. Schiano,et al.  Monoclonal antibody HCV‐AbXTL68 in patients undergoing liver transplantation for HCV: Results of a phase 2 randomized study , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[148]  R. Cortese,et al.  Cell Entry of Hepatitis C Virus Requires a Set of Co-receptors That Include the CD81 Tetraspanin and the SR-B1 Scavenger Receptor* , 2003, Journal of Biological Chemistry.

[149]  J. McKeating,et al.  Hepatitis C virus entry: beyond receptors , 2012, Reviews in medical virology.

[150]  F. Penin,et al.  Characterization of Fusion Determinants Points to the Involvement of Three Discrete Regions of Both E1 and E2 Glycoproteins in the Membrane Fusion Process of Hepatitis C Virus , 2007, Journal of Virology.

[151]  D. Burton,et al.  Rational antibody-based HIV-1 vaccine design: current approaches and future directions. , 2010, Current opinion in immunology.

[152]  Christopher T. Jones,et al.  A Hepatitis C Virus (HCV) Vaccine Comprising Envelope Glycoproteins gpE1/gpE2 Derived from a Single Isolate Elicits Broad Cross-Genotype Neutralizing Antibodies in Humans , 2013, PloS one.

[153]  T. Baumert,et al.  Hepatitis C virus entry. , 2013, Current topics in microbiology and immunology.

[154]  G. Szabo,et al.  Identification and Characterization of Broadly Neutralizing Human Monoclonal Antibodies Directed against the E2 Envelope Glycoprotein of Hepatitis C Virus , 2009, Journal of Virology.

[155]  Charles M. Rice,et al.  Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus , 2012, Proceedings of the National Academy of Sciences.

[156]  A. Tarr,et al.  Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding , 2006, Journal of Virology.

[157]  P. Schürmann,et al.  Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C , 2007, Proceedings of the National Academy of Sciences.

[158]  R. Thimme,et al.  Adaptive immune responses in hepatitis C virus infection. , 2013, Current topics in microbiology and immunology.

[159]  S. Ciesek,et al.  Hepatitis C Virus Hypervariable Region 1 Modulates Receptor Interactions, Conceals the CD81 Binding Site, and Protects Conserved Neutralizing Epitopes , 2010, Journal of Virology.

[160]  R. Cortese,et al.  The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus , 2002, The EMBO journal.

[161]  A. Tarr,et al.  Cross-genotype characterization of genetic diversity and molecular adaptation in hepatitis C virus envelope glycoprotein genes. , 2007, The Journal of general virology.

[162]  K. Meyer,et al.  Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function , 2013, Journal of Virology.

[163]  J. Sodroski,et al.  Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies , 1994, Journal of virology.

[164]  S. Frøland,et al.  Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin. , 1994, The New England journal of medicine.

[165]  A. Tarr,et al.  Determination of the human antibody response to the epitope defined by the hepatitis C virus-neutralizing monoclonal antibody AP33. , 2007, The Journal of general virology.

[166]  S. Ray,et al.  Cross-Genotype Immunity to Hepatitis C Virus , 2004, Journal of Virology.

[167]  C. Rice,et al.  Neutralizing antibody response during acute and chronic hepatitis C virus infection. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[168]  Charles M. Rice,et al.  A genetically humanized mouse model for hepatitis C virus infection , 2011, Nature.

[169]  O. Laeyendecker,et al.  Acute Hepatitis C Virus Structural Gene Sequences as Predictors of Persistent Viremia: Hypervariable Region 1 as a Decoy , 1999, Journal of Virology.

[170]  Margaret Hellard,et al.  High incidence of hepatitis C virus reinfection in a cohort of injecting drug users , 2008, Hepatology.

[171]  Ying-hua Chen,et al.  Neutralizing antibodies , 2002, Immunologic research.

[172]  C. Bréchot.  Hepatitis C virus , 1996, Digestive Diseases and Sciences.

[173]  A. Tarr,et al.  Hepatitis C Patient-Derived Glycoproteins Exhibit Marked Differences in Susceptibility to Serum Neutralizing Antibodies: Genetic Subtype Defines Antigenic but Not Neutralization Serotype , 2011, Journal of Virology.

[174]  J. Dubuisson,et al.  Hepatitis C Virus E2 Has Three Immunogenic Domains Containing Conformational Epitopes with Distinct Properties and Biological Functions , 2004, Journal of Virology.

[175]  M. Houghton,et al.  Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection , 2001, Hepatology.

[176]  H. Thomas,et al.  Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients , 1998, Hepatology.

[177]  F. Cosset,et al.  Clearance of Genotype 1b Hepatitis C Virus in Chimpanzees in the Presence of Vaccine-Induced E1-Neutralizing Antibodies , 2011, The Journal of infectious diseases.

[178]  D. Rowlands,et al.  Expression of hepatitis C virus (HCV) structural proteins in trans facilitates encapsidation and transmission of HCV subgenomic RNA. , 2009, The Journal of general virology.

[179]  G. Leroux-Roels,et al.  A candidate vaccine based on the hepatitis C E1 protein: tolerability and immunogenicity in healthy volunteers. , 2004, Vaccine.