title: Combinatorial library-based profiling of the antibody response against hepatitis C virus in humans.
abstract: The antibody response plays a crucial role against hepatitis C virus (HCV) infection, and our understanding of this intricate progress in vivo is far from complete. We previously reported a novel and robust technique based on a large combinatorial viral antigen library displayed on the surface of the yeast Saccharomyces cerevisiae, allowing comprehensive profiling of polyclonal antibody responses in vivo in both qualitative and quantitative terms. Here, we report the generation and application of a combinatorial library of HCV strain JFH1 envelope glycoprotein to profile the antibody response in four HCV chronically infected individuals. By systematic analysis of the location and frequency of antigenic fragments along the JFH1 envelope glycoprotein, we showed that the major binding antibody response was targeted to E2 (80.9-99.8 %), whilst that against E1 was relatively small (0.3-19.0 %). A total of five major antigenic domains (D1-D5) were identified: one was within E1 and an additional four within E2, despite substantial variability among the different individuals. However, serum absorption with the yeast clones containing the antigenic domain D1 resulted in more reduction in neutralizing antibody activity against pseudotyped HCV than those in E2, suggesting that E1 contains additional neutralizing epitopes. Our results have provided additional insights into the HCV-specific antibody response in humans and should assist in a better understanding of protective antibody immunity and in guiding the development of effective vaccines and therapeutics against HCV infection.
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Kan
authors.initials: K
authors.lastname: Luo
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qing
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Xuanling
authors.initials: X
authors.lastname: Shi
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Comprehensive AIDS Research Center and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, PR China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015723:Gene Library; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D018937:Hepatitis C Antibodies / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins