Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels

乙型肝炎表面抗原 免疫学 抗体 病毒学 乙型肝炎 接种疫苗 人口 抗原 等离子体电池 B细胞 医学 生物 病毒 乙型肝炎病毒 环境卫生
作者
Ruoyao Qi,Rao Fu,Lei Xing,Jinhang He,Yao Jiang,Liang Zhang,Yangtao Wu,Siling Wang,Xueran Guo,Feng Chen,Meifeng Nie,Man Yang,Yiyi Chen,Jing Zeng,Jingjing Xu,Hualong Xiong,Mujin Fang,Yuqiong Que,Youliang Yao,Ying-Bin Wang,Jiali Cao,Huiming Ye,Yali Zhang,Zizheng Zheng,Tong Cheng,Jun Zhang,Xu Lin,Quan Yuan,Tianying Zhang,Ningshao Xia
出处
期刊:Journal of Hepatology [Elsevier]
被引量:1
标识
DOI:10.1016/j.jhep.2023.12.032
摘要

Background & Aims

Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B.

Methods

A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice.

Results

Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance.

Conclusions

Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice.

Impact and implications

Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
3秒前
烟花应助liweiDr采纳,获得10
3秒前
jindou完成签到,获得积分10
4秒前
7秒前
8秒前
充电宝应助lulu采纳,获得10
9秒前
一二三完成签到 ,获得积分10
9秒前
Rosie关注了科研通微信公众号
10秒前
望月暑生发布了新的文献求助10
11秒前
xuey发布了新的文献求助10
12秒前
一二完成签到 ,获得积分10
12秒前
14秒前
14秒前
慕青应助兜有米采纳,获得10
15秒前
sci梦发布了新的文献求助10
17秒前
18秒前
19秒前
余鱼鱼发布了新的文献求助10
19秒前
不二仙完成签到,获得积分10
21秒前
23秒前
24秒前
闲出屁国公主完成签到 ,获得积分10
24秒前
24秒前
liweiDr发布了新的文献求助10
25秒前
科研通AI2S应助不二仙采纳,获得10
26秒前
zhangyafei发布了新的文献求助10
28秒前
28秒前
29秒前
香蕉觅云应助dsdingding采纳,获得10
29秒前
脑洞疼应助认真的彩虹采纳,获得10
30秒前
30秒前
31秒前
Rosie发布了新的文献求助10
32秒前
所所应助sci梦采纳,获得10
32秒前
32秒前
32秒前
LJL发布了新的文献求助10
36秒前
刘十一发布了新的文献求助10
37秒前
RCheng完成签到,获得积分10
39秒前
慕青应助郝幻嫣采纳,获得30
41秒前
高分求助中
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Handbook of Qualitative Cross-Cultural Research Methods 600
Chen Hansheng: China’s Last Romantic Revolutionary 500
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3139294
求助须知:如何正确求助?哪些是违规求助? 2790157
关于积分的说明 7794200
捐赠科研通 2446581
什么是DOI,文献DOI怎么找? 1301284
科研通“疑难数据库(出版商)”最低求助积分说明 626124
版权声明 601109