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

Efficacy evaluation through human trials is crucial for advancing a candidate vaccine to clinics. Next-generation sequencing (NGS) can be used to quantify B cell repertoire response and trace antibody lineages during vaccination. Here, we demonstrated this application with a case study of Hecolin, the licensed vaccine for hepatitis E virus (HEV). Four subjects were administered the vaccine following a standard three-dose schedule. Vaccine-induced antibodies exhibited a high degree of clonal diversity, recognized five conformational antigenic sites of the genotype 1 HEV p239 antigen, and cross-reacted with other genotypes. Unbiased repertoire sequencing was performed for seven time points over six months of vaccination, with maturation pathways characterized for a set of vaccine-induced antibodies. In addition to dynamic repertoire profiles, NGS analysis revealed differential patterns of HEV-specific antibody lineages and highlighted the necessity of the long vaccine boost. Together, our study provides a quantitative strategy for vaccine evaluation in small-scale human studies.