Quantitative evaluation of protective antibody response induced by hepatitis E vaccine in humans

Gui-Ping Wen,Zi-Zheng Zheng,Ning-Shao Xia,Shao-Wei Li,Jiang Zhu,Zi-Min Tang,Dong Ying,Linling He,Si-Ling Wang,Jia-Xin Chen,Shou-Jie Huang,Xu Zhang,Wen-Xin Luo,Ying-Bin Wang,Chang Liu,Yuan-Zhi Chen,Xiaohe Lin,Jun Zhang,Zi-Hao Chen

doi:10.1038/s41467-020-17737-w

Gui-Ping Wen, Zi-Zheng Zheng + Show 17 more

Open Access

https://doi.org/10.1038/s41467-020-17737-w

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Abstract

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®, 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.

Highlights

Efficacy evaluation through human trials is crucial for advancing a vaccine candidate to clinics
Positive antiHEV immunoglobulin G (IgG) seroconversion was observed at day 30 after the first dose, with anti-hepatitis E virus (HEV) IgG levels ranging from 0.17 World Health Organization (WHO) unit per mL (WU per mL) to 0.89 WU per mL (Fig. 1b)
The results indicated that the HEV vaccine, Hecolin®, can induce a robust immune response with rapid development of p239(1)-specific antibodies in all four donors

Summary

Introduction

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 We demonstrate this application with a case study of Hecolin®, the licensed vaccine for hepatitis E virus (HEV). Serological analysis of vaccinated humans has been performed to assess anti-HEV immunoglobulin G (IgG) titer, anti-HEV IgG avidity, and epitope specificity[14,18,22] It remains to be determined whether the vaccine derived from p239(1) can protect against all four genotypes with the same efficacy. We utilize a quantitative strategy to characterize the vaccine-induced antibody response by combining antigen-specific single-cell sorting and antibody cloning with NGS-based antibody-repertoire profiling and lineage-tracing analysis. Our study has provided valuable insights into the HEV vaccine mechanism and will have important implications for future vaccine evaluation in humans

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