Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults Previously Vaccinated with a Live-Attenuated Herpes Zoster Vaccine: A Phase III, Group-Matched, Clinical Trial

Abstract

BackgroundHerpes zoster (HZ), caused by reactivation of varicella-zoster virus (VZV), typically manifests as a dermatomal rash and can lead to postherpetic neuralgia (PHN). HZ and PHN risk increase with age. Efficacy against HZ induced by a live-attenuated zoster vaccine (ZVL; Merck) declines following vaccination (21% in years 5–12 post-vaccination). To ensure protection, revaccination can be considered. Therefore, we assessed immunogenicity and safety of HZ/su, a non-live candidate vaccine containing VZV glycoprotein E (gE) subunit and AS01B adjuvant system (GSK), in adults previously vaccinated with ZVL ≥5 years before, (HZ-PreVac) compared with adults not vaccinated with ZVL (HZ-NonVac).MethodsIn this phase III, group-matched, open, multicenter study (NCT02581410), 2 parallel groups of adults ≥65 years of age (YOA) received 2 HZ/su doses 2 months apart. A co-primary objective was to compare humoral immune responses 1 month post-dose 2 (M3) in the 2 groups (non-inferiority criterion: upper limit [UL] of the 95% confidence interval [CI] for HZ-NonVac/HZ-PreVac adjusted anti-gE antibody geometric mean concentration [GMC] ratio <1.5). Humoral and cellular immune responses were evaluated at various time points. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post each dose, respectively. Serious AEs (SAEs), HZ cases and potential immune-mediated diseases (pIMDs) will be recorded until study end. Here, we present data up to M3, as the study is still ongoing.Results430 participants were vaccinated. M3 humoral immune responses in HZ-PreVac were non-inferior to those in HZ-NonVac and the co-primary objective was met as the UL of the 95% CI of the adjusted GMC ratio was 1.17 (Table 1). In addition, there were no apparent differences in CD4[2+] T-cell frequencies between groups (Figure 1). No clinically meaningful differences between frequencies of solicited AEs, unsolicited AEs or SAEs in the 2 groups were observed (Table 2). No SAEs considered vaccine-related by investigators, no suspected HZ cases and no pIMDs were reported up to M3.ConclusionHZ/su vaccination in adults ≥65 YOA who previously received ZVL stimulates strong immune responses and does not raise safety concerns.FundingGlaxoSmithKline Biologicals SADisclosures K. Grupping, GSK group of companies: Employee, Salary; L. Campora, GSK group of companies: Employee, Salary; M. Douha, GSK group of companies: Employee, Salary; T. C. Heineman, GSK group of companies: Consultant and Shareholder, Consulting fee; N. P. Klein, GSK group of companies: Investigator, Grant recipient sanofi pasteur: Investigator, Grant recipient; Merck & Co: Investigator, Grant recipient; MedImmune: Investigator, Grant recipient; Protein Science: Investigator, Grant recipient; Pfizer: Investigator, Grant recipient; H. Lal, Pfizer: Employee and Shareholder, Salary and Stock as part of compensation; GSK group of companies: Employee at the time of study and Shareholder, Salary and Stock as part of compensation; J. Peterson, GSK group of companies: Investigator, Principal investigator fees; L. Oostvogels, GSK group of companies: Employee and Shareholder, Salary and Shares