A randomized lot-to-lot immunogenicity consistency study of the candidate zoster vaccine HZ/su

Vaccine. 2017 Dec 4;35(48 Pt B):6700-6706. doi: 10.1016/j.vaccine.2017.10.017. Epub 2017 Oct 24.

Abstract

Background: The risk of developing herpes zoster (HZ) increases with age and is thought to be associated with a decrease in cell-mediated immunity in older adults. The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) recombinant subunit vaccine (HZ/su) showed >90% efficacy in the prevention of HZ when administered in adults ≥50 years of age. Here we aim to evaluate immunogenicity consistency of 3 different HZ/su vaccine lots and to assess safety of these lots.

Methods: This multicenter, phase III, double-blind, randomized study (NCT02075515), assessed lot-to-lot consistency in terms of immunogenicity of HZ/su and also assessed safety of these lots. Participants aged 50 years or older were randomized (1:1:1) to receive 2 doses of HZ/su, 2 months apart, from 1 out of 3 randomized HZ/su lots (Lots A, B and C). Humoral immunogenicity was assessed pre-vaccination and 1 month post-second vaccination by anti-gE antibody enzyme-linked immunosorbent assay. Lot-to-lot consistency was demonstrated if the 2-sided 95% confidence intervals of the anti-gE geometric mean concentration ratio between all lot pairs were within 0.67 and 1.5. Solicited symptoms were recorded within 7 days and unsolicited adverse events (AEs) within 30 days after each vaccination. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were reported until study end (12 months post-second vaccination).

Results: Of 651 participants enrolled in the study, 638 received both doses of the HZ/su vaccine and 634 completed the study. Humoral immune responses were robust and consistency between 3 manufacturing lots was demonstrated. The incidence of solicited symptoms, unsolicited AEs and SAEs was comparable between all lots. Three fatal SAEs, 1 in each lot, were reported, none of which were considered vaccine-related by investigator assessment. Two out of the 8 reported pIMDs were considered vaccine-related by the investigator.

Conclusion: The three HZ/su manufacturing lots demonstrated consistent immunogenicity. No safety concerns were identified. Clinical trial registry number: NCT02075515 (ClinicalTrials.gov).

Keywords: Glycoprotein E; Immunogenicity; Lot consistency; Recombinant subunit vaccine; Safety; Varicella-zoster virus.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Aged
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Herpes Zoster / prevention & control*
  • Herpes Zoster Vaccine / adverse effects*
  • Herpes Zoster Vaccine / genetics
  • Herpes Zoster Vaccine / immunology*
  • Herpes Zoster Vaccine / standards
  • Herpesvirus 3, Human / immunology
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunogenicity, Vaccine*
  • Male
  • Middle Aged
  • Vaccination / adverse effects*
  • Vaccination / statistics & numerical data
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / standards
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / standards
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Herpes Zoster Vaccine
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • glycoprotein E, varicella-zoster virus

Associated data

  • ClinicalTrials.gov/NCT02075515