Safety and Immunogenicity of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in HIV-Infected Adults: A Phase 1/2a Randomized, Placebo-Controlled Study

Berkowitz, Elchonon M.; Moyle, Graeme; Stellbrink, Hans‐Jürgen; Schürmann, Dirk; Kegg, Stephen; Stoll, Matthias; Idrissi, Mohamed El; Oostvogels, Lidia; Heineman, Thomas C.; Brockmeyer, Norbert H.; DeJesus, Edwin; Eßer, Stefan; Hawkins, Trevor; Lalezari, Jacob; Orkin, Chloe; Schneider, Stefan

doi:10.1093/infdis/jiu606

Cited by 182 publications

(159 citation statements)

References 25 publications

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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.…”

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confidence: 88%

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

Lal²,

et al. 2016

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“…gE is abundantly expressed on the surface of varicellazoster virions and by infected cells, and appears to be a major target for VZV-specific CD4 + T-cell responses [24]. HZ/su was also designed to address the burden of herpes zoster in the immunocompromised population [25,26], where live-attenuated vaccine is contraindicated [27].…”

Section: Plasmodium and Varicella-zoster Virus: Two Pathogens With Comentioning

confidence: 99%

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Didierlaurent

Laupèze

Pasquale

et al. 2016

Expert Review of Vaccines

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Introduction: Adjuvants are used to improve vaccine immunogenicity and efficacy by enhancing antigen presentation to antigen-specific immune cells with the aim to confer long-term protection against targeted pathogens. Adjuvants have been used in vaccines for more than 90 years. Combinations of immunostimulatory molecules, such as in the Adjuvant System AS01, have opened the way to the development of new or improved vaccines. Areas covered: AS01 is a liposome-based vaccine adjuvant system containing two immunostimulants: 3-O-desacyl-4ʹ-monophosphoryl lipid A (MPL) and the saponin QS-21. Here we describe studies investigating the mode of action of AS01, and consider the role of AS01 in enhancing specific immune responses to the antigen for selected candidate vaccines targeting malaria and herpes zoster. The effects of AS01 are rapid and transient, being localized to the injected muscle and draining lymph node. AS01 is efficient at promoting CD4 + T cell-mediated immune responses and is an appropriate candidate adjuvant for inclusion in vaccines targeting viruses or intracellular pathogens. Expert commentary: AS01 activity to enhance adaptive responses depends on synergistic activities of QS-21 and MPL. AS01 adjuvantation shows good prospects for use in new vaccines targeted to populations with challenging immune statuses and against diseases caused by complex pathogens. ARTICLE HISTORY

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“…The safety and efficacy of the HZ/su vaccine within immunocompromised groups has been investigated in two phase I/II single-blind randomized trials among autologous hematopoietic cell transplant recipients with hematologic malignancies [120] and among antiretroviral treated or naïve HIV-infected adults with CD4 T cell counts ranging from 50 to >500 cells/ml [121]. Both trials showed immunogenicity similar to that in healthy patients and no vaccination-related serious adverse effects were reported.…”

Section: Zoster Vaccine – Unresolved Questionsmentioning

confidence: 99%

Varicella and herpes zoster vaccine development: lessons learned

Warren‐Gash

Forbes

Breuer

2017

Expert Review of Vaccines

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Introduction: Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines’ efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.

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Safety and Immunogenicity of an Adjuvanted Herpes Zoster Subunit Candidate Vaccine in HIV-Infected Adults: A Phase 1/2a Randomized, Placebo-Controlled Study

Cited by 182 publications

References 25 publications

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

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

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Varicella and herpes zoster vaccine development: lessons learned

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