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.

Characteristics Peripheral Blood IgG and IgM Heavy Chain Complementarity Determining Region 3 Repertoire before and after Immunization with Recombinant HBV Vaccine

“…Furthermore, the family source sequences and CDR3 sequences demonstrated heterogeneity [23]. Our findings also consistent with Chang’s report, they used HTS to characterize the H chain CDR3 sequences in paired siblings of 4 families in which only one member of each pair had chronic HBV infections, they reported that vaccination induced significant increases of H chain CDR3 cluster diversities among siblings without hepatitis B [24]. Our studies showed that the 3 healthy individuals shared a small number of CDR3 sequences before and after the immunization.…”

Shared IgG Infection Signatures vs. Hemorrhage-Restricted IgA Clusters in Human Dengue: A Phenotype of Differential Class-Switch via TGFβ1

“…The protocol in recruiting dengue subjects (Table 1 ; ND 5 , SD 1-7 , and HD 1-7 ) was approved by the Institutional Review Board of Kaohsiung Medical University Hospital. Some of non-dengue controls (Table 1 ; ND 1-4 ) were from a previous study ( 13 ), the protocol of which was approved by both the Institutional Review Board of National Health Research Institutes and the Institutional Review Board of En Chu Kong Hospital. Study methods were carried out in accordance with the relevant guidelines.…”

“…In this study, we adapted a selection heuristic of antibody repertoires that was developed to characterize carrier children of chronic hepatitis B and vaccination responses of healthy siblings on the platform of NGS ( 13 ). After reproducing the same result of the infection signature in the hepatitis B data set by the new pipeline, we applied the renewed scheme to a public data set of dengue fever from Mexico.…”

Inferring B cell specificity for vaccines using a Bayesian mixture model

“…Vaccination provides a controlled and easily administered stimulus that can be used to study this complex system [7]. An increase in clonality has been observed in the post-vaccination BCR repertoire, which has been related to the proliferation of B cells and the production of active plasma cells [8][9][10][11][12][13][14]. An increase in the sequences shared between individuals, referred to as the public repertoire or stereotyped BCRs, has also been observed, and there is mounting evidence that this public repertoire is at least partly due to convergent evolution in different individuals responding to the same stimulus [10,[14][15][16][17][18].…”