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

Clin Microbiol Infect. 2019 Sep;25(9):1133-1139. doi: 10.1016/j.cmi.2019.01.015. Epub 2019 Jan 31.

Abstract

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

Methods: A total of 126 participants aged ≥18 years were randomly assigned to receive the hepatitis E virus 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. Sixty-two participants in the accelerated group and 63 in the routine group received at least one dose of vaccine; 57 and 63 participants received all three doses and were 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), and the geometric mean concentrations (GMCs) were 8.51 WHO units/mL (95% CI 6.73-10.76) in the accelerated group and 9.67 WHO units/mL (95% CI 7.67-12.20) in the routine group. The ratio of the accelerated group GMC to the routine group GMC 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 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 with 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 (Clinical Trial Registration. NCT03168412).

Keywords: Accelerated vaccination; Clinical trial; Hepatitis E vaccine; Immunogenicity; Safety.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Hepatitis Antibodies / blood
  • Hepatitis E / prevention & control*
  • Hepatitis E virus / immunology*
  • Humans
  • Immunization Schedule*
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • Safety
  • Vaccination / adverse effects
  • Vaccination / standards
  • Viral Hepatitis Vaccines / administration & dosage*
  • Viral Hepatitis Vaccines / adverse effects
  • Viral Hepatitis Vaccines / standards
  • Young Adult

Substances

  • Hepatitis Antibodies
  • Viral Hepatitis Vaccines

Associated data

  • ClinicalTrials.gov/NCT03168412