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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.

Background: Herpes zoster may significantly impact quality of life (QoL) in older adults. The recombinant zoster vaccine (RZV) is efficacious in adults aged ≥50 and older and is associated with increased reactogenicity compared to placebo. We report here on the impact of reactogenicity of the second RZV dose on the QoL and physical functioning (PF) of vaccine recipients, and summarize findings following both doses.Method: In this single-arm study, 401 adults aged ≥50 and older were enrolled to receive two RZV doses 2 months apart. Change in mean Short Form Survey-36 (SF-36) PF and EuroQol-5 Dimension (EQ-5D) scores, reactogenicity, safety, productivity loss, and healthcare resource utilization were evaluated.Results: In total, 391 (97.5%) participants received dose 2. Post-dose 2, the most common solicited local symptoms were injection site pain (75.1%), erythema (22.4%), and swelling (13.9%), and the most common systemic symptoms were fatigue (46.3%), headache (37.5%), and myalgia (32.9%). Grade 3 solicited (local and systemic) adverse events were reported by 61 (15.6%) participants and were associated with a transient clinically significant decrease in SF-36 PF score on Days 1-2 post-dose 2 that recovered by Day 3. Overall, no clinically important reduction in mean SF-36 PF scores was observed from baseline to post-dose 2 (mean change -0.4), and no quality-adjusted-life-year loss was recorded.Conclusions: Overall, QoL and PF of RZV vaccinees were not affected by vaccine-related reactogenicity. A transient reduction was observed in the first 2 days after RZV vaccination in individuals with Grade 3 adverse events. No safety concerns were identified. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: Frail participants are often under‐represented in randomized trials, raising questions about outcomes of interventions in real‐world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes. DESIGN/SETTING: Data from two previously conducted phase III randomized trials of RZV were pooled. These two parent trials were conducted concurrently at the same study sites using the same methods. PARTICIPANTS/INTERVENTION: In the two parent studies, participants aged ≥50 years (ZOE‐50 study) and ≥70 years (ZOE‐70 study), respectively, were randomized 1:1 to receive two doses of RZV or placebo. MEASUREMENTS: In the current ZOE‐Frailty study (NCT03563183), a frailty index was created using previously validated methods. Clinical outcomes assessed by frailty status included vaccine efficacy, immunogenicity, reactogenicity, and safety. RESULTS: Of 29,305 participants from the pooled ZOE‐50 and ZOE‐70 total vaccinated cohort, 92% were included in this study. Mean age was 68.8 years; 58.1% were women; 45.6% were pre‐frail and 11.3% frail. The percentage of frail participants increased with age from 5.7% aged 50–59 years to 22.7% aged ≥80 years. RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non‐frail: 95.8% (95% confidence interval = 91.6–98.2), pre‐frail: 90.4% (84.4–94.4), frail: 90.2% (75.4–97.0)). The RZV group demonstrated robust anti‐gE antibody and gE‐specific CD42+ responses, with mean concentrations remaining above pre‐vaccination levels at least 3 years post‐dose two, in all frailty subgroups. In the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty. CONCLUSION: The relatively nonrestrictive inclusion/exclusion criteria in the parent ZOE studies resulted in a range of participants that included frail and pre‐frail older adults. RZV significantly reduced the risk of herpes zoster across all frailty subgroups. [ABSTRACT FROM AUTHOR]