title: Network Signatures of IgG Immune Repertoires in Hepatitis B Associated Chronic Infection and Vaccination Responses.
abstract: The repertoire of IgG antibody responses to infection and vaccination varies depending on the characteristics of the immunogen and the ability of the host to mount a protective immune response. Chronic hepatitis B virus (HBV) infections are marked by persistent infection and immune tolerance to vaccination. This disease offers a unique opportunity to discover key repertoire signatures during infection and in response to vaccination. Complementarity determining region 3 of an antibody heavy chain (CDR-H3) has a major impact on the antigenic specificity of an antibody. We used next-generation sequencing to characterize the CDR-H3 sequences in paired siblings of 4 families in which only one member of each pair had chronic HBV infection. Blood samples were obtained before and 2 weeks after HBV vaccination. The analysis revealed a huge network of sequence-related CDR-H3 clones found almost exclusively among carriers. In contrast, vaccination induced significant increases of CDR-H3 cluster diversities among siblings without hepatitis B. Several vaccination-associated clone clusters were identified. Similar findings of vaccination-associated clone networks were observed in healthy adults receiving HBV boosters. These strategies can be used to identify signatures of other infectious diseases and accelerate discoveries of antibody sequences with important biomedical implications.
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Pediatrics, En Chu Kong Hospital, Sanxia 23702, Taiwan.
authors.forename: Hui-Chung
authors.initials: HC
authors.lastname: Kuan
authors.affiliation: Institute of Statistics, National Tsing Hua University, Hsin-Chu 30043, Taiwan.
authors.forename: T C
authors.initials: TC
authors.lastname: Hsieh
authors.affiliation: Institute of Statistics, National Tsing Hua University, Hsin-Chu 30043, Taiwan.
authors.forename: K H
authors.initials: KH
authors.lastname: Ma
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Taiwan.
authors.forename: Chung-Hsiang
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Taiwan.
authors.forename: Wei-Bin
authors.initials: WB
authors.lastname: Hsu
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Taiwan.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
authors.affiliation: Institute of Statistics, National Tsing Hua University, Hsin-Chu 30043, Taiwan.
authors.forename: Anne
authors.initials: A
authors.lastname: Chao
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 35053, Taiwan.|Pediatrics, En Chu Kong Hospital, Sanxia 23702, Taiwan.
authors.forename: Hong-Hsing
authors.initials: HH
authors.lastname: Liu
mesh_terms: D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male
chemical_list: D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G