TY - JOUR
T1 - Adjuvanted recombinant zoster vaccine in adult autologous stem cell transplant recipients
T2 - polyfunctional immune responses and lessons for clinical practice
AU - Stadtmauer, Edward A.
AU - Sullivan, Keith M.
AU - El Idrissi, Mohamed
AU - Salaun, Bruno
AU - Alonso Alonso, Aránzazu
AU - Andreadis, Charalambos
AU - Anttila, Veli Jukka
AU - Bloor, Adrian J.C.
AU - Broady, Raewyn
AU - Cellini, Claudia
AU - Cuneo, Antonio
AU - Dagnew, Alemnew F.
AU - Di Paolo, Emmanuel
AU - Eom, Hyeon Seok
AU - González-Rodríguez, Ana Pilar
AU - Grigg, Andrew
AU - Gunther, Andreas
AU - Heineman, Thomas C.
AU - Jarque, Isidro
AU - Kwak, Jae Yong
AU - Lucchesi, Alessandro
AU - Oostvogels, Lidia
AU - Polo Zarzuela, Marta
AU - Schuind, Anne E.
AU - Shea, Thomas C.
AU - Sinisalo, Ulla Marjatta
AU - Vural, Filiz
AU - Yáñez San Segundo, Lucrecia
AU - Zachée, Pierre
AU - Bastidas, Adriana
N1 - Funding Information:
The authors declare the following financial relationships: During the conduct of the study, CA, and EAS report grants from the GSK group of companies (GSK); VJA reports Phase III study compensation from GSK to the research institute; and KMS reports a grant and personal fees from GSK and a grant from NIAID and NIH awarded to Duke University. Outside the submitted work, VJA reports study grants from Pfizer, and personal fees from Astellas, MSD, Pfizer, Roche, and Unimedic; AGr has served on the Advisory Boards of Bristol Myers Squibb, Gilead, MSD, Novartis, Roche, and Takeda; AGu reports personal fees from Celgene, Takeda, Janssen-Cilag, Novartis, Teva, and Jazz; and KMS reports personal fees from Kiadis Pharmaceutical, and Roche Genentech. During the design, initiation, conduct of the study and/or interpretation of the data, AB, AFD, EDP, MEI, TCH, LO, BS, and AES were employees of GSK. They also own shares in the GSK group of companies. AB, AFD, and LO are currently employed by the Bill & Melinda Gates Medical Research Institute, Mithra Pharmaceuticals, and CureVac AG, respectively. TCH and LO are inventors on a patent owned by GSK and relevant to RZV. Outside the submitted work, TCH was a paid consultant for GSK. AAA, AJCB, RB, CC, AC, HE, APGR, IJ, JYK, AL, MPZ, TCS, UMS, FV, LYSS, and PZ have no conflicting financial relationships to disclose. The authors declare no other non-financial relationships and activities or conflicts of interest.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - adjuvanted recombinant zoster vaccine
KW - Autologous hematopoietic stem cell transplant
KW - cell-mediated immunity
KW - humoral immune response
KW - polyfunctionality
KW - vaccine efficacy
U2 - 10.1080/21645515.2021.1953346
DO - 10.1080/21645515.2021.1953346
M3 - Article
AN - SCOPUS:85112769313
SN - 2164-5515
JO - HUMAN VACCINES & IMMUNOTHERAPEUTICS
JF - HUMAN VACCINES & IMMUNOTHERAPEUTICS
ER -
