Characterization of the TCR β Chain Repertoire in Peripheral Blood from Hepatitis B Vaccine Responders and Non-Responders

Abstract

Background: Hepatitis B (HepB) vaccination can effectively prevent the prevalence of hepatitis B virus (HBV) infection. However, the incidence of vaccination failure is about 5~10% and the underlying molecular mechanisms are poorly understood. T cells have an essential role in the recipient's immune response to vaccine, which could be elucidated by high-throughput sequencing (HTS) and bioinformatics analysis. Methods: We conducted HTS of the T cell receptor β chain (TRB) complementarity-determining region 3 (CDR3) repertoires in eighteen positive responders (responders) and 10 negative responders (non-responders) who all had HepB vaccination, the repertoire features of BV, BJ and V-J genes and their diversity, respectively, were compared between the positive and negative responders using the Mann-Whitney test. Moreover, the relatively conserved motifs in CDR3 were revealed and compared to those in the other group's report. Results:The diversity of TRB CDR3 and the frequencies of BV27 and BV7-9 are significantly increased for HepB vaccine responders compared to those in non-responders. The motifs of CDR3s in BV27/J1-1, BV27/J2-5, and BV7-9/J2-5, respectively, were most expressed as "NTE", "QETQ", and "GG-Q (E)-ETQ". Moreover, the motif "KLNSPL" was determined in nearly 80% CDR3s in BV27/J1-6 from HepB vaccine responders for the first time. Conclusion: Our results present the comprehensive profiles of TRB CDR3 in the HepB vaccine responders and non-responders after standard vaccination protocol and determine the relatively conservative motifs of CDR3s that may respond to the HepB vaccine. Further results suggest that the profile of TRB repertoire could distinguish the HepB vaccine responders from non-responders and provide a new target for optimizing and improving the efficiency of the HepB vaccine.

The prognosis and immune repertoire characteristics of HBsAg and anti-HBs double positivity chronic hepatitis B patients

“…Zhan et al identi ed motifs such as "CASSLG" and "GAGPLT" as a consensus sequence potentially linked to anti-HBs antibody production, and motifs like "NYGYTF" and "NSPLHF" as potential HBV-speci c motifs, providing new insights for HBV vaccination and treatment [39] . Furthermore, nearly 80% of "KLNSPL," "GNEQ," and "LLRWYGY" in BV27/J1-6 of TCR CDR3 was found in responders to the hepatitis B vaccine [40] . Our study, for the rst time, revealed that DP and HC groups shared predominant motifs for TCR CDR3 V(D)J combinations, while the RP group exhibits entirely distinct motifs, suggesting that motifs like "VCLCKS" and "CRRRRK" in the RP group may be effective in the anti-HBV response (Fig.…”

“…reported increased frequencies of motifs such as "NTE," "QETQ," and "GG-Q (E)-ETQ" in respondents to the hepatitis B vaccine compared to non-respondents in TRB repertoire analysis [40] . Moreover, we found that "xxxxxW" was speci cally expressed in the IGH V(D)J combinations of the RP group, suggesting its potential as a protective motif against anti-HBV infection (Fig.…”

Upregulated CD8+ MAIT cell differentiation and KLRD1 gene expression after inactivated SARS-CoV-2 vaccination identified by single-cell sequencing

“…To elucidate the molecular basis of the 5~10% failure rate of the hepatitis B vaccine, Yang et al. ( 48 ) conducted high-throughput sequencing and bioinformatics analysis of TRB CDR3 repertoires and found that the diversity of TRB CDR3 was significantly increased in responders compared to non-responders, which suggested that individuals with increased TCR diversity had better vaccine responses. Our results showed an increased TCR diversity after vaccination, suggesting that the SARS-CoV-2 inactivated vaccine elicits adaptive T cell immunity that can facilitate the recognition of multiple antigens.…”

T-Cell Receptor β Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs

“…Moreover, the motif “NYGYTF” and “NSPLHF” could be the HBV-specific motif, and the motif “GAGPLT” may relate to anti-HBs production, which paves the way for HBV vaccination and treatment. Yang et al have reported that the motifs “NTE,” “QETQ,” and “GG-Q (E)-ETQ” were expressed mostly in BV27 and BV7-9, which are significantly increased in hepatitis B vaccine responders compared to those in non-responders in the TRB repertoire analysis of hepatitis B vaccine response [ 34 ]. Furthermore, the motif “KLNSPL” was found in nearly 80% of CDR3s in BV27/J1-6 from hepatitis B vaccine responders.…”