Herpes Zoster Vaccine

Almost 100 % of the adult population are latently infected with varicella zoster virus (VZV), which manifests as chickenpox during the primary infection usually occurring in childhood, and as herpes zoster (shingles) during reactivation. It is believed that reactivation occurs when VZV-specific cellular immune responses decline due to immunosuppressive conditions or immunosenescence, and less VZV-specific T cells are detectable in the old compared to young adults [78]. The incidence of herpes zoster increases with age and rises from 1 to 3 per 1000 person-years in young adults to

  • 6- 10 per 1000 person-years in persons aged 60-70 years. The incidence is even higher in the very old [3]. The lifetime risk of a herpes zoster infection is approximately 50 % among those who reach 85 years of age [79]. Post-herpetic neuralgia (PHN) is characterized by persistent pain for months or even years after acute herpes zoster and is the most common complication of herpes zoster. PHN can have a dramatic impact on activities of daily living, frequently leading to loss of independence and institutionalization in the old [80]. A vaccine containing a high dose of the live- attenuated Oka-strain, the strain which is also used as a paediatric vaccine against chickenpox, was licensed for vaccination of the old in 2006. This vaccine induces antibody and T cell responses [81], and its clinical efficacy has been demonstrated in a large double-blind placebo-controlled study [82] in persons over 60 years of age. Compared to placebo the incidence of herpes zoster was reduced by 51.3 % (95 % CI 44.2-57.6) and the incidence of PHN by 66.5 % (95 % CI 44.5-79.2) in the vaccinated population. Whereas the protective effect against PHN was independent of age, the efficacy against herpes zoster was age-dependent and decreased to only 37.6 % in persons older than 69 years. The duration of the protection has been studied in followup studies demonstrating a decrease in vaccine efficacy with each year after vaccination, and reporting an estimated vaccine efficacy of 21.1 % (95 % CI 20.9-30.4) for the prevention of herpes zoster and 35.4 % (95 % CI 8.8-55.8 %) for PHN in years
  • 7- 10 [83]. These results raise the question of optimal age for vaccination. The vaccine is licensed for adults over the age of 50 years, but most countries recommend vaccination at age 60. A clinical trial evaluating the safety and immunogenicity of a second dose of vaccine 10 years later is currently being performed (ClinicalTrials.gov,

NCT01245751) and will provide information about whether a booster dose of herpes zoster vaccine is beneficial. Despite ACIP (Advisory Committee on Immunization Practices) recommendations having been in place for several years, the uptake of the vaccine remains low in the US, reaching approximately 20 % in managed care populations, and even less in the general population [84].

The incidence of herpes zoster is also high in immunocompromised patients, e.g. after transplantation, in cancer patients, and in HIV-positive individuals, as cell-mediated immunity to VZV is impaired in these patients. As the current herpes zoster vaccine contains live-attenuated virus, it cannot be used in immunocompromised patients due to safety issues [85]. A novel, inactivated vaccine against herpes zoster containing the viral glycoprotein E in combination with the liposome-based AS01B adjuvant system (MPL and QS21) has been developed, and phase I/II studies have demonstrated safety and immunogenicity in hematopoietic cell transplant recipients [86], in HIV-patients [87] and in older adults [88, 89]. Overall clinical efficacy against herpes zoster was 97.2 % (95 % CI 93.7-99.0, p < 0.001) in a phase III randomized placebo-controlled trial including more than 15,000 adults over the age of 50. Remarkably, vaccine efficacy in adults who were 70 years of age or older, was similar to the younger study cohorts [90]. This vaccine might replace the live-attenuated herpes zoster vaccine in the future depending on further data provided by ongoing clinical trials including information on long-term protection and the potential need for booster doses.

 
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