Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older

Abstract

BACKGROUNDA trial involving adults 50 years of age or older showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01 B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older . METHODSThis randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTSIn ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONSIn our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. ( 1020T h e ne w e ngl a nd jou r na l o f m e dicine H erpes zoster, or shingles, results from the reactivation of latent varicellazoster virus (VZV) and typically manifests as a vesicular, painful dermatomal rash.

Varicella and herpes zoster vaccine development: lessons learned

“…HZ/su consists of 50 µg of recombinant VZV antigen (glycoprotein E) which directs the immune response to the virus itself, combined with the AS01B adjuvant system to stimulate T cell immunity to recombinant proteins [106]. As described in detail elsewhere [106], two very large multicenter-blinded RCTs reported that, among participants who had received two doses of Hz/su, VE against zoster was 97.2% (95% CI 93.7–99.0%) for adults aged ≥50 years [107] and 89.8% (95% CI 84.2–93.7%) for those aged ≥70 years [108]. In a pre-specified analysis of data pooled from both trials, the VE against PHN was 88.8% (95% CI 68.7–97.1%).…”

“…First, the VE of HZ/su against zoster is substantially higher overall (91% [108] versus 51.3% [79]). Second, theoretically HZ/su has greater potential for use in immunosuppressed patients, as it is not a live vaccine so does not pose risks of triggering varicella- or zoster-like illnesses; it has shown promise in phase I/II trials in severely immunocompromised patients [106].…”

“…Second, theoretically HZ/su has greater potential for use in immunosuppressed patients, as it is not a live vaccine so does not pose risks of triggering varicella- or zoster-like illnesses; it has shown promise in phase I/II trials in severely immunocompromised patients [106]. Third, unlike Zostavax, the HZ/su vaccine is equally effective among older age groups; HZ/su has a VE against zoster incidence of 89.1% among those ≥80 years [108], compared to a VE of 37.6% among those aged ≥70 years for Zostavax [79]. …”

A new herpes zoster subunit vaccine for older adults

“…These adverse reactions tended to be transient, mild to moderate reactions, with a median duration of 2-3 days for injection site reactions and 1-2 days for systemic reactions. Systemic reactions were more frequently reported in HZ/su vaccine recipients (53.0%) 5 than in recipients of live attenuated vaccine (25%) 8 . Importantly, rates of serious adverse events, immune-mediated disease and deaths did not differ between HZ/su vaccine and placebo groups.…”

“…In the study, known as ZOE-70, 13,900 participants with a mean age of 75.6 years were recruited from 18 countries and randomly allocated to receive either two doses of an investigational herpes zoster subunit vaccine (HZ/su; GSK vaccines) or placebo 5 . The new vaccine contained 50 µg of recombinant VZV glycoprotein E and the liposome-based AS01b adjuvant system, which enhances CD4+ T-cell and humoral immune responses to recombinant proteins.…”