BACKGROUND: Herpes zoster (HZ) vaccines should provide durable protection against HZ and HZ-related complications. We report the final analysis of a long-term follow-up (LTFU) study (ZOE-LTFU) including 11 years of follow-up after primary vaccination with recombinant zoster vaccine (RZV). METHODS: ZOE-LTFU (NCT02723773) was an open-label, phase 3b study following participants of two phase 3 trials, ZOE-50 and ZOE-70. ZOE-LTFU started approximately 5 years post-vaccination in ZOE-50/70 and participants were followed for 6 years. The primary objective was to assess vaccine efficacy (VE) against HZ during ZOE-LTFU. Secondary objectives included VE against HZ from 1 month post-dose 2 in ZOE-50/70 until end of ZOE-LTFU, VE against post-herpetic neuralgia (PHN) and non-PHN complications, immunogenicity, and long-term safety. The VE calculation used a historical control constructed with ZOE-50/70 placebo data. FINDINGS: VE was assessed in the modified total vaccinated cohort (n = 7273 [mean age 67·3 years at first vaccination]). During ZOE-LTFU, VE was 79·8% (95% confidence interval [CI]: 73·7, 84·6) and 73·2% (95% CI: 62·9, 80·9) against HZ in participants ≥50 and ≥70 years at first vaccination, respectively, and was 87·5% (95% CI: 64·8, 96·8) against PHN and 91·7% (95% CI: 43·7, 99·8) against other HZ-related complications in participants ≥50 years. From 1 month post-dose 2 in ZOE-50/70 to the end of ZOE-LTFU, VE against HZ was 87·7% (95% CI: 84·9, 90·1) in participants ≥50 years and sustained at 82·0% (95% CI: 63·0, 92·2) in the eleventh year post-vaccination. Humoural and cell-mediated immune responses plateaued at over 5-fold and ∼7-fold, respectively, above pre-vaccination levels in ZOE-50/70. No RZV-related serious adverse events occurred. INTERPRETATION: Efficacy of RZV against HZ and associated complications remained high through 11 years post-vaccination, indicating sustained clinical benefit. FUNDING: The funder of the study was GSK who was involved in study design, data collection, data analysis, data interpretation, writing of the report, and the decision to submit for publication.

• Keywords
• Herpes zoster, Long-term follow-up, Post-herpetic neuralgia, Recombinant zoster vaccine,
• Publication type
• Journal Article MeSH

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,
• MeSH
• Adjuvants, Immunologic MeSH
• Herpes Zoster * prevention & control   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Aged MeSH
• Vaccines, Synthetic MeSH
• Herpes Zoster Vaccine * MeSH
• Herpesvirus 3, Human MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Vaccines, Synthetic MeSH
• Herpes Zoster Vaccine * MeSH