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 is an ongoing follow-up study (NCT02723773) evaluating persistence of efficacy and immune responses for six additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at ≥50 years of age in two pivotal efficacy trials (ZOE-50/70). 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 onwards, and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of four assessed activation markers) frequencies from Y5 post-vaccination onwards. 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 for the evaluation of 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 during this follow-up study through the interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells had plateaued throughout this follow-up study up to the interim analysis, at ~6-fold above pre-vaccination levels. Conclusion 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 seven years post-vaccination.

Long-term efficacy data for the recombinant zoster vaccine: impact on public health and cost effectiveness in Germany

“… 19–21 The primary clinical trial results from the interim analysis of the ZOE-LTFU study suggests that the VE estimates at 8 years post vaccination were 84.3% overall. 10 In this manuscript, we have provided more granular data from that study demonstrating that VE estimates at 8 years post vaccination were 87.5% in individuals aged 50–69 and 78.9% in individuals aged ≥70 YOA (see supplementary Table S1). Szucs et al, in a review of HZ vaccine cost-effectiveness manuscripts noted that a limitation of most modeling studies was that outdated input data were used.…”

“…An interim analysis of ZOE-LTFU, following up the original ZOE study populations, presented the VE estimates out to 8 years following initial vaccination. 10 Details of the study design and methodology are provided in Boutry et al 10 We used the observed ZOE-LTFU clinical trial VE analysis by year separated into the age groups 50–69 and ≥70 YOA (see supplementary Table S1) to estimate the VE at time 0 (i.e. take) and slope (annual waning) of efficacy over time using a linear regression model.…”

“…An interim analysis of the ZOE-LTFU study presenting the vaccine efficacy (VE) estimates out to 8 years post-initial vaccination was recently published. 10 …”

Cost-Effectiveness Analysis Update of the Adjuvanted Recombinant Zoster Vaccine in Japanese Older Adults

“…Additionally, the previous cost-effectiveness analysis of RZV in Japanese adults does not reflect the most up-to-date parameters of RZV efficacy and waning rate. Interim results from the ongoing long-term follow-up (LTFU) of the ZOE-50 and ZOE-70 studies (ZOE-LTFU; NCT02723773) have shown that RZV efficacy remained high for up to 8 years post-vaccination [ 19 ]. When the updated vaccine efficacy results were incorporated into a Markov model, RZV was found to improve public health and cost-effectiveness results compared with previous analyses in the German population aged ≥ 50 years [ 20 ], although the effects in the Japanese population have not been explored.…”

Effect of universal varicella vaccination and behavioral changes against coronavirus disease 2019 pandemic on the incidence of herpes zoster

“…It is not clear whether the cause of this difference is due to the booster immunization route of natural varicella infection or subcutaneous injection, or the wild or attenuated vaccine strain of VZV, or immunoreactivity of the target age groups between< 50 and> 50. The HZ-preventive effect of another HZ-preventive vaccine, gE-based Shingrix®, was sustained for at least 7 years [24] . Since the HZ incidence continues to rise, the preventive effect of varicella contact on HZ seems to be as persistent as Shingrix®.…”