Decline in Varicella‐Zoster Virus (VZV)–Specific Cell‐Mediated Immunity with Increasing Age and Boosting with a High‐Dose VZV Vaccine

Abstract

The safety and immunogenecity of a booster dose of live attenuated varicella-zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years old, who had already received a VZV vaccine >5 years before. This repeat booster dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay. Prevaccination responses decreased as a function of increasing age but were detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related to prevaccination values. Although there was a significant correlation between the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay.

Vaccination against Herpes Zoster and Postherpetic Neuralgia

“…The SPS confirmed the increased incidence and severity of HZ in older individuals, which is associated with a progressive age-related decline in VZV-CMI [3,18,21,[26][27][28][29][30][31][32]. Because recent studies, as well as data from individuals in the SPS, indicate that VZV vaccines can boost VZV-CMI in older individuals [21,32,[37][38][39], we believe that the observed efficacy of the investigational HZ vaccine reflects its ability to boost VZV-CMI in vaccinated subjects.…”

“…Because recent studies, as well as data from individuals in the SPS, indicate that VZV vaccines can boost VZV-CMI in older individuals [21,32,[37][38][39], we believe that the observed efficacy of the investigational HZ vaccine reflects its ability to boost VZV-CMI in vaccinated subjects. The investigational HZ vaccine was well tolerated.…”

“…Observations during the past 4 decades have supported the thesis that T cellmediated immunity to VZV (VZV-CMI) is the major determinant of the risk and severity of HZ [2,9,21,[24][25][26][27][28][29][30][31][32]. The increased incidence and severity of HZ and PHN observed in older adults are closely correlated with a progressive age-related decline in VZV-CMI, whereas levels of antibody to VZV remain relatively constant with increasing age [2,9,21,24,[27][28][29][30][31][32].…”

“…Subsequent studies have demonstrated that Oka-derived VZV vaccines can elicit a significant increase in VZV-CMI in immunocompetent older adults [32,[37][38][39] and can reduce the incidence and severity of HZ in recipients of bone marrow allografts [40,41]. These observations led us to hypothesize that immunization of older adults with live attenuated Oka VZV vaccine would boost their waning VZV-CMI and thereby provide protection against HZ and PHN [21,31,42,43].…”

Preventing and managing herpes zoster: key actions to foster healthy aging

“…The incidence of HZ increases with age, mainly because of immunosenescence, which leads to a decline in the response to infection by both the innate and adaptive immune systems. The aging process includes numerous alterations in the immune system including agerelated changes in the T-and B-lymphocyte patterns in conjunction with a reduction in the numbers and efficiency of antigen-presenting cells [49][50][51][52][53][54].…”