Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans
Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans
复制标题
人类戊型肝炎疫苗诱导的保护性抗体反应的定量评估
DOI：
10.1038/s41467-020-17737-w
复制
发表时间：
2020-08-07
影响因子：
16.6
通讯作者：
Xia, Ning-Shao
中科院分区：
文献类型：
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作者：
Wen, Gui-Ping;He, Linling;Xia, Ning-Shao
通过人体试验进行功效评估对于将候选疫苗推向临床至关重要。下一代测序 (NGS) 可用于量化 B 细胞库反应并在疫苗接种过程中追踪抗体谱系。在这里，我们通过 Hecolin (R) 的案例研究来演示这一应用，Hecolin (R) 是获得许可的戊型肝炎病毒 (HEV) 疫苗。四名受试者按照标准的三剂量时间表接种疫苗。疫苗诱导的抗体表现出高度的克隆多样性，识别基因型 1 HEV p239 抗原的五个构象抗原位点，并与其他基因型发生交叉反应。在疫苗接种后六个月内的七个时间点进行无偏见的谱库测序，其成熟途径表征了一组疫苗诱导的抗体。除了动态谱系特征外，NGS 分析还揭示了 HEV 特异性抗体谱系的差异模式，并强调了长期疫苗加强的必要性。总之，我们的研究提出了小规模人体研究中疫苗评估的定量策略。作者提供了四名个体在接种疫苗后六个月内对获得许可的戊型肝炎病毒 (HEV) 疫苗 Hecolin 的人类抗体反应的全面表征。他们展示了疫苗保护背后的不同抗体反应模式。
Efficacy evaluation through human trials is crucial for advancing a vaccine candidate to clinics. Next-generation sequencing (NGS) can be used to quantify B cell repertoire response and trace antibody lineages during vaccination. Here, we demonstrate this application with a case study of Hecolin (R), the licensed vaccine for hepatitis E virus (HEV). Four subjects are administered the vaccine following a standard three-dose schedule. Vaccine-induced antibodies exhibit a high degree of clonal diversity, recognize five conformational antigenic sites of the genotype 1 HEV p239 antigen, and cross-react with other genotypes. Unbiased repertoire sequencing is performed for seven time points over six months of vaccination, with maturation pathways characterize for a set of vaccine-induced antibodies. In addition to dynamic repertoire profiles, NGS analysis reveals differential patterns of HEV-specific antibody lineages and highlights the necessity of the long vaccine boost. Together, our study presents a quantitative strategy for vaccine evaluation in small-scale human studies. The authors provide a comprehensive characterization of the human antibody response to a licensed hepatitis E virus (HEV) vaccine, Hecolin, in four individuals over the course of six months post vaccination. They demonstrate diverse patterns of antibody response underlying the vaccine protection.