1. Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients: polyfunctional immune responses and lessons for clinical practice
- Author
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Stadtmauer, Edward A, Sullivan, Keith M, Idrissi, Mohamed El, Salaun, Bruno, Alonso, Aránzazu Alonso, Andreadis, Charalambos, Anttila, Veli-Jukka, Bloor, Adrian JC, Broady, Raewyn, Cellini, Claudia, Cuneo, Antonio, Dagnew, Alemnew F, Di Paolo, Emmanuel, Eom, HyeonSeok, González-Rodríguez, Ana Pilar, Grigg, Andrew, Guenther, Andreas, Heineman, Thomas C, Jarque, Isidro, Kwak, Jae-Yong, Lucchesi, Alessandro, Oostvogels, Lidia, Zarzuela, Marta Polo, Schuind, Anne E, Shea, Thomas C, Sinisalo, Ulla Marjatta, Vural, Filiz, San Segundo, Lucrecia Yáñez, Zachée, Pierre, and Bastidas, Adriana
- Subjects
Clinical Research ,Rare Diseases ,Cancer ,Immunization ,Prevention ,Clinical Trials and Supportive Activities ,Hematology ,Lymphoma ,Vaccine Related ,Stem Cell Research ,Transplantation ,6.2 Cellular and gene therapies ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Hematopoietic Stem Cell Transplantation ,Herpes Zoster ,Herpes Zoster Vaccine ,Herpesvirus 3 ,Human ,Humans ,Immunity ,Cellular ,Vaccine Efficacy ,Autologous hematopoietic stem cell transplant ,cell-mediated immunity ,polyfunctionality ,humoral immune response ,adjuvanted recombinant zoster vaccine ,vaccine efficacy ,Immunology ,Medical Microbiology ,Pharmacology and Pharmaceutical Sciences ,Virology - Abstract
Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.
- Published
- 2021