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
Authors: Boutry Céline , Hastie Andrew , Diez-Domingo Javier , Tinoco Juan Carlos , Yu Chong-Jen , Andrews Charles , Beytout Jean , Caso Covadonga , Cheng Huey-Shinn , Cheong Hee Jin , Choo Eun Ju , Curiac Dan , Di Paolo Emmanuel , Dionne Marc , Eckermann Tamara , Esen Meral , Ferguson Murdo , Ghesquiere Wayne , Hwang Shinn-Jang , Avelino-Silva Thiago Junqueira , Kosina Pavel , Liu Chiu-Shong , Markkula Jukka , Moeckesch Beate , Murta de Oliveira Cláudia , Park Dae Won , Pauksens Karlis , Pirrotta Paola , Plassmann Georg , Pretswell Carol , Rombo Lars , Salaun Bruno , Sanmartin Berglund Johan , Schenkenberger Isabelle , Schwarz Tino , Shi Meng , Ukkonen Benita , Zahaf Toufik , Zerbini Cristiano , Schuind Anne , Cunningham Anthony L ,   Zoster-049 Study Group, Adams Michael , Ahonen Anitta , Athan Eugene , Barba-Gómez Jose-Fernando , Barbanti Piero , Barberan Elisabeth , Baty Alain , Bengtsson Niklas , Berger-Roscher Juergen , Berndtsson Blom Katarina , Boucher Loïc , Boye Alain , Brault François , Breger Laurie , Brotons Cuixart Carles , Cerna Christine , Cunha Clóvis , Daguzan Benoit , Dahmen Antje , Datta Susan , Giuseppina Desole Maria , Dite Petr , Dutz Jan , Earl John , Ellison William , Eremenko Jurij , Eto Takashi , Farrés Fabré Xavier , Farrington Cecil , André Ferrand Pierre , Finneran Matthew , Francyk David , Freedman Marshall , Freeman George , Gal Peter , Gauthier Jean-Sebastien , Gerlach Beatrice , Gorfinkel Iris , Grigat Christine , Grosskopf Josef , Hamann Monika , Hanrion Pascal , Hartley Paul , Heaton Ken , Himpel-Boenninghoff Agnes , Horacek Thomas , Shu Cheong Hui David , Huong Yieng , Icardi Giancarlo , Illies Gabriele , Irimajiri Junya , Jambrecina Alen , Youl Kim Hyo , Klein Christiane , Kleinecke Uwe , Koenig Hans-Joachim , Kokko Satu , Koskinen Pekka , Kropp Maximilian , Kuroki Rie , Laajalahti Outi , Lachance Pierre , Lee Jacob , Lee Jin-Soo , Levins Peter , Lipetz Robert , Liu Bo , Lundvall Martin , Beth Manning Mary , Martin Frederick , Martínez Piera Pyrene , McNally Damien , McNeil Shelly , Migliorino Guglielmo , Morscher Stephan , Mueller Michael , Kashem Munir Abul , Nakamura Kenjiro , Narejos Pérez Silvia , Naritomi Yuji , Nault Patrice , Luiz Neto José , Núñez López Concepción , Ogata Hiroaki , Olsson Åke , Paavola Pauliina , Patrick Janice , Pérez Vera Mercè , Poder Airi , Poling Terry , Purnell-Mullick Samir , Raad George , Redmond Michael , Remaud Philippe , Riffer Ernie , Robert Patrick , Rodríguez Badia Alex , Luisa Rodríguez de la Pinta Maria , Rosen Robert , Rozen Shari , Saillard Dominique , Sauter Joachim , Schaefer Axel , Schmidt Juergen , Schmitt Bernhard , Schubert Christian , Seppa Ilkka , Kwok Yiu Sha Edmund , Shockey Gerald , Shoffner Sylvia , Sirnela-Rif Elina , Staniscia Tommaso , Sueki Hirohiko , Suzuki Shin , Taminau Denis , Tellier Guy , Terns Riera Manuel , Toma Azhar , Toursarkissian Nicole , Turner Mark , Vilella Morató Anna , Wachter Juergen , Webster Brian , Wilhelm Karl , Wilson Jonathan , Yeo Wilfred , Zahharova Irina 
Published: July 2021

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 &gt;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.