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.

Canadian Center for Vaccinology IWK Health NS Health Dalhousie University Halifax Nova Scotia Canada

Catholic University of Valencia Spain

Centre for Clinical Research Sormland Uppsala University Sweden

Centre for Virus Research Westmead Institute for Medical Research Australia

Centro Medico Sao Francisco Curitiba Brazil

Department of Health Sciences University of Genoa Italy

Dept of Infectious Diseases University Hospital and Faculty of Medicine Hradec Kralove Czech Republic

FISABIO Valencia Spain

GSK London UK

GSK Rockville MD USA

GSK Wavre Belgium

Hakata Clinic Fukuoka Japan

Hospital General de Durango Durango Mexico

Hygiene Unit IRCCS San Martino Policlinico Hospital Genoa Italy

IMA Clinical Research San Antonio San Antonio TX USA

Institute of Laboratory Medicine and Vaccination Centre Klinikum Würzburg Mitte Campus Juliusspital Würzburg Germany

National Taiwan University College of Medicine and National Taiwan University Hospital Taipei Taiwan

Soonchunhyang University Bucheon Hospital South Korea

Tartu University Hospital Tartu Estonia

The Chinese University of Hong Kong Hong Kong China

University of Sydney Institute for Infectious Diseases Faculty of Medicine and Health University of Sydney Australia

Zobrazit více v PubMed

Mueller N.H., Gilden D.H., Cohrs R.J., Mahalingam R., Nagel M.A. Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurol Clin. 2008;26(3):675–697. viii. PubMed PMC

Oxman M.N. Herpes zoster pathogenesis and cell-mediated immunity and immunosenescence. J Am Osteopath Assoc. 2009;109(6 Suppl 2):S13–S17. PubMed

Johnson R.W., Alvarez-Pasquin M.J., Bijl M., et al. Herpes zoster epidemiology, management, and disease and economic burden in Europe: a multidisciplinary perspective. Ther Adv Vaccines. 2015;3(4):109–120. PubMed PMC

Dworkin R.H., Johnson R.W., Breuer J., et al. Recommendations for the management of herpes zoster. Clin Infect Dis. 2007;44(Suppl 1):S1–S26. PubMed

Centers for Disease Control and Prevention Clinical features of shingles (herpes zoster) 2024. https://www.cdc.gov/shingles/hcp/clinical-signs/index.html

Serpell M., Gater A., Carroll S., Abetz-Webb L., Mannan A., Johnson R. Burden of post-herpetic neuralgia in a sample of UK residents aged 50 years or older: findings from the Zoster Quality of Life (ZQOL) study. Health Qual Life Outcomes. 2014;12:92. PubMed PMC

Morrison V.A., Johnson G.R., Schmader K.E., et al. Long-term persistence of zoster vaccine efficacy. Clin Infect Dis. 2015;60(6):900–909. PubMed PMC

Klein N.P., Bartlett J., Fireman B., et al. Effectiveness of the live zoster vaccine during the 10 years following vaccination: real world cohort study using electronic health records. BMJ. 2023;383 PubMed PMC

Tseng H.F., Harpaz R., Luo Y., et al. Declining effectiveness of herpes zoster vaccine in adults aged ≥60 years. J Infect Dis. 2016;213(12):1872–1875. PubMed

Chlibek R., Bayas J.M., Collins H., et al. Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age. J Infect Dis. 2013;208(12):1953–1961. PubMed

Cunningham A.L., Lal H., Kovac M., et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375(11):1019–1032. PubMed

Lal H., Cunningham A.L., Godeaux O., et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087–2096. PubMed

Ocran-Appiah J., Boutry C., Hervé C., Soni J., Schuind A., ZOSTER-056 Study Group Safety of the adjuvanted recombinant zoster vaccine in adults aged 50 years or older. A phase IIIB, non-randomized, multinational, open-label study in previous ZOE-50 and ZOE-70 placebo recipients. Vaccine. 2021;39(1):6–10. PubMed

Boutry C., Hastie A., Diez-Domingo J., et al. 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. Clin Infect Dis. 2022;74(8):1459–1467. PubMed PMC

Strezova A., Diez-Domingo J., Al Shawafi K., et al. Long-term protection against herpes zoster by the adjuvanted recombinant zoster vaccine: interim efficacy, immunogenicity, and safety results up to 10 years after initial vaccination. Open Forum Infect Dis. 2022;9(10) PubMed PMC

Didierlaurent A.M., Laupeze B., Di Pasquale A., Hergli N., Collignon C., Garçon N. Adjuvant system AS01: helping to overcome the challenges of modern vaccines. Expert Rev Vaccines. 2017;16(1):55–63. PubMed

López-Fauqued M., Campora L., Delannois F., et al. Safety profile of the adjuvanted recombinant zoster vaccine: pooled analysis of two large randomised phase 3 trials. Vaccine. 2019;37(18):2482–2493. PubMed

Coplan P.M., Schmader K., Nikas A., et al. Development of a measure of the burden of pain due to herpes zoster and postherpetic neuralgia for prevention trials: adaptation of the brief pain inventory. J Pain. 2004;5(6):344–356. PubMed

United Nations. Department of Economic and Social Affairs World social report 2023: leaving no one behind in an ageing world. 2023. https://www.un.org/development/desa/dspd/wp-content/uploads/sites/22/2023/01/WSR_2023_Chapter_Key_Messages.pdf

Johnson R.W., McElhaney J. Postherpetic neuralgia in the elderly. Int J Clin Pract. 2009;63(9):1386–1391. PubMed PMC

Cohen R., Brabant Y., Oraichi D., et al. P-2345. Recent incidence rate of herpes zoster among immunocompetent adults aged 18 and older in the United States. Open Forum Infect Dis. 2025;12(Suppl 1) doi: 10.1093/ofid/ofae631.2497. DOI

Johnson B.H., Palmer L., Gatwood J., Lenhart G., Kawai K., Acosta C.J. Annual incidence rates of herpes zoster among an immunocompetent population in the United States. BMC Infect Dis. 2015;15:502. PubMed PMC

Oostvogels L., Heineman T.C., Johnson R.W., et al. Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant zoster vaccine: a pooled post-hoc analysis of two parallel randomized trials. Hum Vaccin Immunother. 2019;15(12):2865–2872. PubMed PMC

Gater A., Abetz-Webb L., Carroll S., Mannan A., Serpell M., Johnson R. Burden of herpes zoster in the UK: findings from the zoster quality of life (ZQOL) study. BMC Infect Dis. 2014;14 PubMed PMC

Panatto D., Bragazzi N.L., Rizzitelli E., et al. Evaluation of the economic burden of Herpes Zoster (HZ) infection. Hum Vaccin Immunother. 2015;11(1):245–262. PubMed PMC

Cunningham A.L., Heineman T.C., Lal H., et al. Immune responses to a recombinant glycoprotein E herpes zoster vaccine in adults aged 50 years or older. J Infect Dis. 2018;217(11):1750–1760. PubMed PMC

Hastie A., Catteau G., Enemuo A., et al. Immunogenicity of the adjuvanted recombinant zoster vaccine: persistence and anamnestic response to additional doses administered 10 years after primary vaccination. J Infect Dis. 2021;224(12):2025–2034. PubMed PMC

Dooling K.L., Guo A., Patel M., et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018;67(3):103–108. PubMed PMC

Kim D.K., Riley L.E., Hunter P. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2018. MMWR Morb Mortal Wkly Rep. 2018;67(5):158–160. PubMed PMC

UK Health Security Agency Introduction of Shingrix® vaccine for the whole programme and expansion of eligible cohorts letter. 2023. https://www.gov.uk/government/publications/shingles-vaccination-programme-changes-from-september-2023-letter/introduction-of-shingrix-vaccine-for-the-whole-programme-and-expansion-of-eligible-cohorts-letter

Australian Government. Department of Health Statement on the clinical use of zoster vaccines in adults in Australia. 2022. https://www.health.gov.au/sites/default/files/documents/2022/05/statement-on-the-clinical-use-of-zoster-vaccine-in-older-adults-in-australia.pdf

Parikh R., Widenmaier R., Lecrenier N. A practitioner's guide to the recombinant zoster vaccine: review of national vaccination recommendations. Expert Rev Vaccines. 2021;20(9):1065–1075. PubMed

Centers for Disease Control and Prevention Shingles facts and stats. 2024. https://www.cdc.gov/shingles/data-research/index.html