Yang Ting-Wen, Sun Li-Na, Zhang Ting, Pan Yu-Rong, Li Jun, Li Yang-Yang, Han Zhi-Yong, Sun Wan-Bang, Yao Xin-Sheng, He Xiao-Yan
Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China.
Department of Laboratory Medicine, The Second People's Hospital of Guiyang City, Guiyang, China.
Front Immunol. 2025 Jul 4;16:1587553. doi: 10.3389/fimmu.2025.1587553. eCollection 2025.
This study aimed to investigate the duration of hepatitis B surface antibody (HBsAb) level maintenance and characterize the corresponding IgG-H CDR3 repertoire in volunteers exhibiting either ultra-high or extremely low HBsAb levels following hepatitis B virus (HBV) vaccination.
This study was designed to monitor the longitudinal changes in HBsAb levels at multiple time points post-vaccination in healthy volunteers exhibiting either ultra-high or extremely low antibody responses following HBV vaccination. Furthermore, we employed high-throughput sequencing technology to conduct a comprehensive analysis of the compositional differences in the IgG-H CDR3 repertoire. Peripheral blood samples were collected at four distinct phases: pre-vaccination, post-second vaccination, post-third vaccination, and during the follow-up period, to characterize the dynamic changes in the antibody repertoire.
The longitudinal analysis revealed distinct patterns in antibody response kinetics between the two groups. In the ultra-high responder cohort, a peak HBsAb level (25,354 ± 17,993 mIU/mL) was observed following the second vaccine dose. This was followed by a gradual decline, with mean levels stabilizing at 11,356 ± 9,098 mIU/mL post-third dose and 4,229 ± 2,694 mIU/mL at the 4-year follow-up. The ultra-high hepatitis B surface antibody level group (Group H) exhibited a decrease in IgG-H CDR3 diversity after the second vaccination, followed by an increase after the third vaccination. Compared to the extremely low hepatitis B surface antibody level group (Group L), Group H showed higher characteristic immunoglobulin heavy chain variable region V gene () usage frequencies in the CDR3 repertoire after both vaccinations than before vaccination. Additionally, the average mutation rate of the IgG-H CDR3 repertoire in Group H was slightly higher than that in Group L after the third vaccination. Notably, multiple samples from Group H revealed common conserved CDR3 region motifs associated with HBV, as reported in the literature: "YGLDV", "DAFD", "YGSGS", "GAFDI", and "NWFDP".
The prolonged maintenance of ultra-high antibody levels induced by recombinant HBV vaccines in individuals may be closely related to the characteristic usage and mutation frequency in individual responses. These findings could provide novel insights into the complex mechanisms of HBV vaccines and HBV infection.
本研究旨在调查乙肝疫苗接种后乙肝表面抗体（HBsAb）水平维持的持续时间，并对乙肝病毒（HBV）疫苗接种后出现超高或极低HBsAb水平的志愿者中相应的IgG-H CDR3库进行特征分析。
本研究旨在监测健康志愿者接种疫苗后多个时间点HBsAb水平的纵向变化，这些志愿者在接种HBV疫苗后表现出超高或极低的抗体反应。此外，我们采用高通量测序技术对IgG-H CDR3库的组成差异进行全面分析。在四个不同阶段采集外周血样本：接种前、第二次接种后、第三次接种后以及随访期间,以表征抗体库的动态变化。
纵向分析揭示了两组之间抗体反应动力学的不同模式。在超高反应者队列中，第二次接种疫苗后观察到HBsAb水平峰值（25,354±17,993 mIU/mL）。随后逐渐下降，第三次接种后平均水平稳定在11,356±9,098 mIU/mL，4年随访时为4,229±2,694 mIU/mL。超高乙肝表面抗体水平组（H组）在第二次接种后IgG-H CDR3多样性降低，第三次接种后增加。与极低乙肝表面抗体水平组（L组）相比，H组在两次接种后CDR3库中特征性免疫球蛋白重链可变区V基因（）使用频率均高于接种前。此外，第三次接种后H组IgG-H CDR3库的平均突变率略高于L组。值得注意的是，H组的多个样本显示出与HBV相关的常见保守CDR3区域基序，如文献报道：“YGLDV”、“DAFD”、“YGSGS”、“GAFDI”和“NWFDP”.
重组乙肝疫苗在个体中诱导的超高抗体水平的长期维持可能与个体反应中的特征性使用和突变频率密切相关。这些发现可为乙肝疫苗和乙肝感染的复杂机制提供新的见解。
