Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals

Abstract

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.

Keywords: frail; herpes zoster; older adults; quality of life; subunit vaccine.

Conflict of interest statement

Dr Andrew reports grants from the GSK group of companies (GSK) during the study, as well as grants from GSK, the Canadian Frailty Network, the Canadian Institutes of Health Research, the Foundation for Influenza Epidemiology, and grants and personal fees from Sanofi and Pfizer outside the submitted work. Dr Cunningham reports receiving support from GSK to attend conferences, and for a collaborative discovery science project on the vaccine adjuvant used in RZV outside the submitted work. Dr Levin reports grants and fees for Advisory Board from GSK during the study, and is serving as an Advisory Board member for GSK and Merck. Mr Matthews is a freelance consultant for GSK. Dr Schmader reports grants from GSK during the study. Dr McNeil reports grants, personal fees and support for the conduct of clinical trials from GSK and Pfizer, personal fees and support for the conduct of clinical trials from Sanofi Pasteur, as well as personal fees from Merck outside the submitted work. Dr Kim, Mr Dessart, Dr Riley, Dr Schuind and Dr Curran are employees and Dr Oostvogels is a former employee of GSK. Dr Kim, Dr Schuind, Dr Oostvogels and Dr Curran own GSK stock options or (restricted) shares. Dr Oostvogels is employee of CureVac AG and is inventor on a patent owned by GSK and relevant to RZV.

© 2020 The Authors Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.

Figures

Figure 1

Study population. Abbreviations: HZ, herpes zoster; N, number of participants; QoL, quality of life; TVC, total vaccinated cohort; YOA, years of age.

Figure 2

ZBPI burden of illness by vaccine group and frailty status (modified total vaccinated cohort). Abbreviations: RZV, adjuvanted recombinant zoster vaccine; ZBPI, Zoster Brief PainInventory.

Figure 3

RZV‐induced anti‐glycoprotein E antibody responses: percentage of responders by frailty status (A), GMCs by frailty status (B); and RZV‐induced glycoprotein E‐specific cell‐mediated immunity: percentage of responders by frailty status (C), CD42+frequencies by frailty status (D). Abbreviations: ELISA, enzyme‐linked immunosorbent assay; gE, glycoprotein E; GMC, geometric mean concentration; IU, international units; N, number of participants with available results in each group; Q1/Q3, first and third quartiles; RZV, adjuvanted recombinant zoster vaccine.