Next-generation sequencing analysis of the human T-cell and B-cell receptor repertoire diversity before and after hepatitis B vaccination

Abstract

ABSTRACTThe hepatitis B (HB) vaccine effectively prevents the incidence of hepatitis B virus (HBV) infection. However, vaccine failure occurs in 5–10% of the recipients. The precise mechanisms leading to responsiveness to the HB vaccine are poorly understood. High-throughput sequencing (HTS) may help clarify the immune response to the HB vaccine, so we applied this method to investigate whether the HB vaccine induced a specific change in the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires. We conducted HTS of the TCR β chain and BCR IgG heavy (H) chain complementary determining region 3 (CDR3) repertoires in five volunteers before and after the second and third immunizations with the HB vaccine. The HB surface antibody (HBsAb) levels were >10 mIU/ml after the third vaccination in all five participants. The TCR β chain CDR3 repertoire diversity significantly increased, while the BCR IgG H chain CDR3 repertoire diversity significantly decreased after the second vaccination. Although there was no marked inter-individual variation in terms of the numbers of unique reads, it is possible that the TCR β chain and BCR IgG H chain CDR3 repertoires may have changed within the same numbers of unique reads. Our data failed to identify the specific dominant clones that responded to the HB vaccine. In summary, the TCR β chain CDR3 repertoire diversity significantly increased, while the BCR IgG H chain CDR3 repertoire diversity significantly decreased, after the second HB vaccination. These diversity changes might be associated with a better response to the HB vaccine.