Immunogenicity and safety of an accelerated hepatitis E vaccination schedule in healthy adults: a randomized, controlled, open-label, phase IV trial.

OBJECTIVES: This study aimed to evaluate the immunogenicity and safety of a hepatitis E vaccine using an accelerated vaccination schedule (vaccine doses at 0, 7, and 21 days).

METHODS: A total of 126 participants aged≥18 were randomly assigned to receive the HEV vaccine in either the accelerated group (0, 7 and 21 days) or the routine group (0, 1 and 6 months). Serology samples were obtained at 0, 21, 28, and 51 days and 7 months in the accelerated group or 0, 1, 2 and 7 months in the routine group after the first vaccine injection. Adverse events (AEs) reported during the whole study were analysed.

RESULTS: A total of 126 participants were randomized, 63 for each group. 62 participants in accelerated group and 63 in routine group received at least one dose of vaccine; 57 and 63 participants received all three doses and included in per-protocol set respectively. In the per-protocol population, at 1 month after the last dose (accelerated group at 51 days versus routine group at 7 months), the seropositive rates were both 100% (57/57 and 63/63 respectively), while the geometric mean concentrations (GMCs) were 8.51 Wu/mL (95%CI: 6.73-10.76) in the accelerated group and 9.67 Wu/mL (95%CI: 7.67-12.20) in the routine group. The GMC ratio of the accelerated to the routine was 0.88 (95% CI:0.61-2.17, lower limit of 95% CI > 0.5), indicating that the accelerated vaccination schedule was non-inferior to the routine one. The overall incidence rates of solicited AEs in the accelerated and the routine groups were 32.26% (20/62) and 30.16% (19/63), respectively(p=0.800). Most AEs were moderate.

CONCLUSIONS: An accelerated schedule is safe and provides protective antibodies in a shorter time compared to the routine schedule. The accelerated schedule should be recommended to adults who are travelling on short notice to an HE-endemic area or during an HE outbreak setting (Clinical Trial Registration. NCT03168412).