Immunization to reduce the frequency and severity of herpes zoster and its complications

Herpes zoster (HZ) is a localized disease that results from reactivation of an endogenous varicella-zoster virus (VZV) infection that has persisted in latent form within sensory ganglia following an earlier attack of varicella. The incidence and the severity of HZ and its complications increase with advancing age, and this is temporally associated with an age-related decline in cell-mediated immunity (CMI) to VZV. Information on the cellular site and mechanism of VZV latency and on the events that follow reactivation appears to explain many of the clinical features of HZ and to provide a pathophysiologic basis for the presumption that immunity to VZV plays a critical role in limiting the frequency and consequences of VZV reactivation. The close temporal correlation between the decline in VZV-specific CMI and the increased frequency and severity of HZ and its complications in older individuals suggests that HZ may actually develop because VZV-specific CMI falls below some critical threshold. The development of a live attenuated varicella vaccine provides a means of stimulating VZV-specific CMI and thus of determining its role in the pathogenesis of HZ. Levin and his colleagues have demonstrated that waning VZV-specific CMI in elderly persons can be stimulated by varicella vaccine to levels typical of those observed in younger persons, in whom the incidence and severity of HZ are much reduced. Thus the stage is set for a large placebo-controlled clinical trial that will test directly the hypothesis that restoration of waning CMI to VZV will reduce the frequency and severity of HZ and its complications in the elderly.