Immune senescence and vaccines to prevent herpes zoster in older persons

https://doi.org/10.1016/j.coi.2012.06.002Get rights and content

Varicella-zoster virus (VZV) T-cell-mediated immunity (VZV-CMI) in older persons prevents latent VZV in sensory neurons from reactivating to cause herpes zoster. VZV-CMI declines greatly with aging, but can be restored by the licensed zoster vaccine. However, the vaccine-induced boost in VZV-CMI (which determines the efficacy of the vaccine) is a function of the age of the vaccinee, and the duration of this boost wanes with time. Both factors influence the value of this vaccine. To understand these aging effects, limited information about the phenotypic and functional differences in VZV-CMI in old and young persons are reviewed, as well as the reversal of these differences by vaccination. Based on information from these studies some potential approaches to improving prevention of herpes zoster are discussed.

Highlights

► Latent VZV is maintained in sensory neurons because of VZV-specific T-cell immunity. ► This immunity declines with age – the number/function of early effectors and effector memory. ► The loss of this T-cell immunity correlates with the occurrence of herpes zoster. ► A herpes zoster vaccine can restore this immunity and prevent herpes zoster. ► Suggestions are offered to improve the efficacy of zoster vaccine.

Section snippets

Background

Four vaccines are recommended for persons ≥60 years old [1]. In general their responses to these vaccines are significantly less robust than responses by younger vaccinees – in magnitude, duration, and quality of the response, and usually in terms of efficacy [2]. Thus, measuring vaccine-induced responses within this age group is an important technique for characterizing immune senescence and investigating mechanisms of age-related immune dysfunction. Such studies highlight the practical result

Varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI) prevents HZ

The basis for active immunization to prevent HZ is very different from that described for other vaccines recommended for older people. HZ represents reactivation of latent infection with VZV, which infects most individuals in childhood (as varicella) and persists life-long in neurons in ganglia of cranial nerves and the peripheral sensory nervous system [7, 8]. Extensive and definitive immunologic and clinical evidence (patients with certain inborn immunologic defects or after iatrogenic immune

Efficacy endpoints

The currently licensed HZ vaccine contains live, attenuated VZV that induces both VZV-CMI (measured most often as CD4+ responses) and VZV-specific antibody. The rationale for developing this vaccine was that reversing the decline of VZV-CMI with immunization would protect against HZ [9, 25••]. The efficacy of this vaccine in preventing HZ was 51% in vaccinees ≥60 years old, and the effect of age on this protection is evident when efficacy is stratified by age (Table 1). However, this

Improving HZ vaccines

It is apparent that the zoster vaccine-induced responses in many vaccinees are insufficient. It is noteworthy that HZ, which is a strong immunizing event, appears to provide protection against a second attack of HZ for 5 years or less, indicating a problem with immune memory [35], and the follow-up studies (described above) confirm a significant waning zoster vaccine efficacy over a 5-year interval.

Even if we knew the essential age-related deficits for protection to HZ, it is unlikely that

Conclusions

Although empiric approaches are described that might enhance the protective effects of zoster vaccine, developing a more effective vaccine with longer duration of protection will require more information on immune correlates of protection. In this quest, the phenotype, proliferative capacity, and persistence of CD8+ memory cells should be evaluated after zoster vaccine administration, at different ages, as well as the extent of VZV-specific T-cell regulation in vaccinees.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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