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., El Idrissi, Mohamed, Salaun, Bruno, Alonso Alonso, Aranzazu, Andreadis, Charalambos, Anttila, Veli-Jukka, Bloor, Adrian J. C., Broady, Raewyn, Cellini, Claudia, Cuneo, Antonio, Dagnew, Alemnew F., Di Paolo, Emmanuel, Eom, HyeonSeok, Gonzalez-Rodriguez, Ana Pilar, Grigg, Andrew, Gunther, Andreas, Heineman, Thomas C., Jarque, Isidro, Kwak, Jae-Yong, Lucchesi, Alessandro, Oostvogels, Lidia, Polo Zarzuela, Marta, Schuind, Anne E., Shea, Thomas C., Sinisalo, Ulla Marjatta, Vural, Filiz, Yanez San Segundo, Lucrecia, Zachee, Pierre, Bastidas, Adriana, and ZOE-SCT Study Grp Collaborators
- Subjects
Autologous hematopoietic stem cell transplant, adjuvanted recombinant zoster vaccine, cell-mediated immunity, humoral immune response, polyfunctionality, vaccine efficacy - 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