The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70

Abstract

Background: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination.

Methods: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination.

Results: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels.

Conclusions: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

Keywords: adjuvanted recombinant zoster vaccine; immune response persistence; long-term efficacy.

Figure 1.

Study design of the pivotal phase 3 clinical trials (ZOE-50 and ZOE-70) and current long-term follow-up study. ^#Pre-vaccination blood sample and 2 RZV doses 2 months apart. *Collected from subsets of participants for humoral and cell-mediated immunity assessment. Abbreviations: RZV, adjuvanted recombinant zoster vaccine; ZOE-50, pivotal phase 3 clinical trial of RZV in adults aged ≥50 years; ZOE-70, pivotal phase 3 clinical trial of RZV in adults aged ≥70 years.

Figure 2.

Study cohorts. Abbreviations: ATP, according-to-protocol; CMI, cell-mediated immunity; HZ, herpes zoster; mTVC, modified total vaccinated cohort; RZV, adjuvanted recombinant zoster vaccine; ZOE-50, pivotal phase 3 clinical trial of RZV in adults aged ≥50 years; ZOE-70, pivotal phase 3 clinical trial of RZV in adults aged ≥70 years.

Figure 3.

Persistence of humoral and cell-mediated immune responses to RZV in the ZOE-50 and ZOE-70 studies and the current follow-up study up to the data lock point for the interim analysis (according-to-protocol cohort for immunogenicity persistence). A, Anti-gE antibody GMCs. B, Frequencies of CD4[2+] T cells. *Data not shown because only 3 participants had available results for this analysis. Abbreviations: CD4[2+] T cells, CD4 T cells expressing at least 2 of 4 assessed activation markers: interferon-γ, interleukin-2, tumor necrosis factor-α, and CD40 ligand; Q1 and Q3, first and third quartiles, respectively; CI, confidence interval; gE, glycoprotein E; GM, geometric mean; GMC, geometric mean concentration; N, number of participants with available results; RZV, adjuvanted recombinant zoster vaccine; ZOE-50, pivotal phase 3 clinical trial of RZV in adults aged ≥50 years; ZOE-70, pivotal phase 3 clinical trial of RZV in adults aged ≥70 years.

Figure 4.

Plain language summary. Abbreviation: GSK, GlaxoSmithKline.