Safety and Immunogenicity of an AS01-adjuvanted Varicella-zoster Virus Subunit Candidate Vaccine Against Herpes Zoster in Adults &gt;=50 Years of Age

Chlíbek, Roman; Bayas, José M.; Collins, Harry; Pinta, María Luisa Rodriguez de la; Ledent, Edouard; Mols, Johann; Heineman, Thomas C.

doi:10.1093/infdis/jit365

Cited by 130 publications

(104 citation statements)

References 19 publications

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“…53 IL-6, another cytokine that plays a key role in the differentiation of the Th17 cells, 88,89 is induced by AS01 B -adjuvanted vaccines but to a much lower extent by AS03 A -adjuvanted vaccines. 60 Therefore, other adjuvants such as AS01 B which has been shown to induce a potent T-cell response with different types of antigens, [90][91][92] could enhance the Th1/Th17 immune response. Additionally, mucosal (intranasal) administration of the vaccine may be an alternative route to induce a Th17 response.…”

Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03_Badjuvant: Results of a randomized phase I trial

Levy

Licini²,

Haelterman³

et al. 2015

Human Vaccines & Immunotherapeutics

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We assessed the safety, reactogenicity and immunogenicity of a staphylococcal vaccine combining capsular polysaccharides types 5 and 8 (CPS5/8), conjugated to tetanus toxoid (TT), with mutated detoxified a-toxin (AT) and clumping factor A (ClfA). In this phase I, randomized, placebo-controlled, observer-blind trial (NCT01160172), 88 healthy 18-to 40-year-olds received CPS5-TT/CPS8-TT/AT/ClfA vaccine (5/5/10/10 mg or 10/10/30/30 mg dose, each with or without AS03 B adjuvant) or saline, at months 0, 1, 6. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 d post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded throughout the study. Humoral and antigen-specific CD4 C /CD8C T-cell immunity were assessed from Day (D) 0 to D540 post-vaccination. The most frequently reported solicited local and general AEs were pain (78.6%-100% of subjects), fatigue (36.4%-93.3% of subjects post-dose 1-2) and headache (20%-44.4% of subjects post-dose 3). Overall, 4 SAEs and 2 potential immune-mediated diseases (pIMDs) (none fatal or vaccine-related) were reported. For each antigen, pre-vaccination seropositivity rates were high (85.7%-100%) and geometric mean concentrations (GMCs) in vaccine recipients sharply increased from D0 to D14, then plateaued to study end. Exploratory group comparisons suggested higher GMCs with higher dosage, without AS03 B effect. Vaccine-induced antibodies were functional (CPS5 opsonophagocytic assays, and AT/ClfA inhibition assays). AT-and ClfA-specific CD4C T-cells with Th0/Th1 cytokine profile were induced at low levels (median <0.05%) by each formulation (intracellular cytokine staining). In conclusion, no safety concerns were identified and each vaccine formulation induced robust humoral immune responses after the first vaccine dose.

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Section: Discussionmentioning

confidence: 99%

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03_Badjuvant: Results of a randomized phase I trial

Levy

Licini²,

Haelterman³

et al. 2015

Human Vaccines & Immunotherapeutics

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“…2,18,19 An investigational herpes zoster subunit vaccine (HZ/su; GSK Vaccines) containing VZV glycoprotein E and the AS01 B adjuvant system is being evaluated for the prevention of herpes zoster and postherpetic neuralgia in adults 50 years of age or older. [20][21][22][23][24][25] A previous trial (Zoster Efficacy Study in Adults 50 Years of Age or Older showed that HZ/su had a vaccine efficacy against herpes zoster of 97.2%, which was consistent across all age groups. 26 Although 24% of the participants in ZOE-50 were 70 years of age or older, the trial was not intended to definitively assess vaccine efficacy against herpes zoster or postherpetic neuralgia in this age group.…”

mentioning

confidence: 89%

“…Solicited reports of injection-site and systemic reactions were more common among HZ/su recipients than among placebo (saline) recipients, a finding consistent with results of previous studies. 23,25,26 The reactions were generally mildto-moderate in intensity and were transient, and neither their frequencies nor their severity increased significantly after the second dose. * Reports within 7 days after vaccination in the reactogenicity subgroup (a randomly selected subgroup of age-stratified participants) were solicited reports of injection-site reactions (pain, redness, and swelling) and systemic reactions (fatigue, fever, gastrointestinal symptoms, headache, myalgia, and shivering).…”

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confidence: 98%

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

Lal²,

et al. 2016

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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.

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“…Phase I and II studies established that two doses of HZ/su containing 50 μg of recombinant VZV glycoprotein E administered 1 or 2 months apart were well tolerated and induced much more robust VZV-specific and VZV glycoprotein E-specific CD4 + T cell and antibody responses than vOka 161,162 . Two large Phase III placebocontrolled efficacy trials have been recently completed in individuals aged ≥50 years and in individuals aged ≥70 years 163,164 .…”

Section: Preventionmentioning

confidence: 99%

Varicella zoster virus infection

Suzuki

Suga²,

Asano³

2015

Nat Rev Dis Primers

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Safety and Immunogenicity of an AS01-adjuvanted Varicella-zoster Virus Subunit Candidate Vaccine Against Herpes Zoster in Adults >=50 Years of Age

Abstract: NCT00802464.

Cited by 130 publications

References 19 publications

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03_Badjuvant: Results of a randomized phase I trial

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03_Badjuvant: Results of a randomized phase I trial

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

Varicella zoster virus infection

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Safety and Immunogenicity of an AS01-adjuvanted Varicella-zoster Virus Subunit Candidate Vaccine Against Herpes Zoster in Adults >=50 Years of Age

Abstract: NCT00802464.

Cited by 130 publications

References 19 publications

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03Badjuvant: Results of a randomized phase I trial

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03Badjuvant: Results of a randomized phase I trial

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

Varicella zoster virus infection

Contact Info

Product

Resources

About

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03_Badjuvant: Results of a randomized phase I trial

Safety and immunogenicity of an investigational 4-componentStaphylococcus aureusvaccine with or without AS03_Badjuvant: Results of a randomized phase I trial