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- Chlibek, Roman, et al.
(author)
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Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults : A phase II, randomized, controlled study
- 2014
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In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 32:15, s. 1745-1753
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Journal article (peer-reviewed)abstract
- Background: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system ASO1(B). Methods: In this phase II, single-blind, randomized, controlled study, adults aged >= 60 years (N = 714) received one dose of 100 mu g gE/AS01(B), two doses, two months apart, of 25, 50, or 100 mu g gE/AS01(B), or two doses of unadjuvanted 100 mu g gE/saline. Frequencies of CD4(+) T cells expressing >= 2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. Results: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01(B) formulations than after one dose of 100 mu g gE/AS01(B) or two doses of 100 mu g gE/saline. Frequencies were comparable after two doses of 25, 50, or 100 mu g gE/AS01g. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100 mu g gE/AS01(B) and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01(B) formulations were similar but greater than with gE/saline. Conclusions: The three formulations of gE/AS01(B) were immunogenic and well tolerated in adults aged >= 60 years. Two vaccinations with gE/AS01(B) induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).
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| 2. |
- Cunningham, A. L., et al.
(author)
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Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older
- 2016
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 375:11, s. 1019-1032
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Journal article (peer-reviewed)abstract
- BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) 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 (ZOE-70). METHODS This 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. RESULTS In 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. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.govnumbers, NCT01165177 and NCT01165229.)
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