Safety and immunogenicity of thiomersal-free recombinant hepatitis E vaccine: A randomized, double-blind, active-controlled study

Abstract

Introduction: The first recombinant hepatitis E vaccine (Escherichia Coli), Hecolin® (Xiamen Innovax, China), was approved for people aged ≥16 years. Innovax has developed a thiomersal-free formulation process change according to the requirement of 2020 Chinese Pharmacopoeia. This study aimed to evaluate the safety and immunogenicity of the thiomersal-free hepatitis E vaccine compared with the licensed hepatitis E vaccine in people aged ≥16 years.

Clinical trial registration: NCT06564116.

Methods: This was a single-center, randomized, double-blind, active-controlled study conducted in China. Eligible participants were randomly assigned in a 1:1 ratio to the thiomersal-free hepatitis E vaccine group (HEV-TF group) or the hepatitis E vaccine group (HEV group) stratified by sex and age. Each participant received three doses of the vaccine intramuscularly at 0, 1 and 6 months. Safety was evaluated based on adverse events (AEs) occurred within 30 days following each dose, serious adverse events (SAEs) and pregnancy events occurred during the study period. Immunogenicity was evaluated through quantification of anti-HEV IgG in serum samples collected at 0 and 7 months.

Results: A total of 612 eligible participants were enrolled and received at least 1 dose of vaccine. 558 participants were included in the per protocol set for immunogenicity. All participants seroconverted in both groups by month 7. The seroconversion rate difference was 0.00 % (95 % confidence interval [CI] -1.38 to 1.34). The geometric mean concentrations (GMCs) in HEV-TF group and HEV group were 16.57 U/mL and 18.47 U/mL, respectively. The GMC ratio was 0.90 (95 % CI 0.79 to 1.01). The overall AEs rates were similar between the groups (16.88 % vs. 12.50 %). Most of AEs were grade 1 or 2. No vaccine-related SAE occurred during the study period.

Conclusions: The thiomersal-free hepatitis E vaccine demonstrated non-inferior immunogenicity compared with the licensed hepatitis E vaccine Hecolin® and showed an acceptable safety profile.

Keywords: Hepatitis E; Hepatitis E vaccine; Thiomersal.