Varicella-Zoster Virus–Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine

Herpes zoster (HZ) is an often painful neurocutaneous syndrome resulting from reactivation of varicella-zoster virus (VZV) that has remained latent in sensory ganglia after primary VZV infection (varicella) [1–3]. The frequency and severity of HZ and its most common debilitating complication, postherpetic neuralgia (PHN), increase with age [4–9]. This age-related increase in disease correlates closely with the decline in VZV-specific T cell mediated immunity (VZV-CMI) that accompanies aging [10–14]. It is very unlikely that antibodies to VZV play a role in this relationship, because they do not decline with aging [13, 14]. Furthermore, HZ frequently occurs in circumstances when VZV-CMI is depressed while levels of VZV antibody are maintained by intravenous γ-globulin, such as those following hematopoietic stem cell transplantation [15–17] On the basis of these observations, it was hypothesized that HZ might be prevented or attenuated (i.e., less pain and PHN) in elderly individuals if their waning VZV-CMI could be boosted with a VZV vaccine [18–20]. Pilot studies indicated that VZV-CMI could be boosted in subjects ⩾60 years old with live attenuated Oka strain VZV vaccines [13, 14, 21, 22]. Subsequent trials demonstrated the safety and immunogenicity of a high-potency Oka/Merck VZV vaccine in elderly subjects, including persons with diabetes and chronic lung disease, and established the optimal vaccine formulation and potency (M.J. Levin et al., unpublished data) A double-blind, placebo-controlled trial (Veterans Affairs Cooperative Study 403: “The Shingles Prevention Study”) that involved 38,546 subjects ⩾60 years of age demonstrated that a high potency live attenuated Oka/Merck VZV vaccine (hereafter, “zoster vaccine”) significantly reduced the burden of illness due to HZ, understood in terms of a severity-by-duration measure of HZ pain and discomfort (i.e., the vaccine decreased the incidence of HZ and decreased the average severity of HZ in vaccinees who developed HZ), and substantially reduced the incidence of PHN in vaccine recipients [9]. The trial included an immunology substudy in which a subset of subjects had immunologic assessments performed before and after vaccination. We describe here the magnitude and kinetics of VZV-specific immune responses to zoster vaccine measured during the immunology substudy and their possible association with the occurrence of HZ