Long-term protection from naturally acquired immunity against hepatitis E virus reinfection

Figures

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  Fig. 1. Study design and flowchart. In the phase 3 clinical study of the hepatitis E vaccine Hecolin®, 7032 participants from the placebo arm of the immunogenicity subset (participants from Town QD and Town AF) who had valid baseline serostatus data were included in the analysis set for natural infection. Serum samples were collected at baseline (0 m) and scheduled blood collection time points including months 0, 7, 13, 19, 31, 43, 55, 67, 79, 91, and 103, and anti-HEV IgG antibodies were tested. In the PI-A set, the intervals between the paired samples include 6, 7, 12, and 13 months, with a median interval of 12 months. In the OI-A set, the intervals between the two consecutive samples range from 6 to 103 months, with a median interval of 24 months. The presence of HEV infection was determined by the dynamic changes in anti-HEV IgG antibodies across the series of serum samples. Hepatitis E cases were captured through an active hepatitis surveillance system established for the phase 3 clinical trial from 2007 to 2017.

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  Fig. 2. Adjusted protection of pre-existing antibodies against HEV infection. The y-axis in the figure represents the protection rate over the entire follow-up period (from month 0 to the specified time point). The error bars in the figure represent the 95% confidence interval of the protection rate. a In the Precise infection analysis (PI-A) set. b In the Overall infection analysis (OI-A) set. A Poisson regression model was utilized to evaluate the relative risk (RR) of the incidence between the groups. The protection rate (%) was calculated as (1 − RR) ×100. The adjusted protection rate was calculated by including age, sex, and township as covariates in the model. Source data are provided as a Source Data file.

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  Fig. 3. Cumulative incidence of HEV infection. a In the Precise infection analysis (PI-A) set. b In the Overall infection analysis (OI-A) set. Participants were categorized into seven groups based on baseline anti-HEV IgG concentrations: not detectable (green line), [0.077, 0.25) (light blue line), [0.25, 0.5) (dark blue line), [0.5, 1.0) (light purple line), [1.0, 2.5) (dark purple line), [2.5, 5.0) (pink line), and ≥5.0 WU/mL (orange line). “Not detectable” indicates antibody concentrations below the cut-off of 0.077 WU/mL; for example, [0.077, 0.25) represents concentrations ≥0.077 but <0.25 WU/mL, [0.25, 0.5) represents ≥0.25 but <0.5 WU/mL, and so forth. Cumulative HEV infection incidence was shown for the PI-A set within 55 months and for the OI-A set within 103 months. P-value was calculated by the log-rank test for comparison across all groups. These figures of survival analysis (i.e., Kaplan–Meier) were generated using R software, version 4.5.1.