Varicella-Zoster Virus-Specific Cell-Mediated Immune Response Kinetics and Latent Viral Load Depending on Aging

Herpes zoster (HZ), an infection caused by varicella-zoster virus (VZV) reactivation, results from an age-related decline in VZV-specific cell-mediated immunity (CMI). Digital droplet PCR (ddPCR) precisely quantifies latent VZV DNA in the blood, a potential biomarker of subclinical viral reactivation and its association with HZ risk. This study assessed VZV-specific CMI, latent viral burden, and humoral immunity in healthy adults according to age. We prospectively enrolled healthy adults aged between 40 and 80 years between February and April 2024. VZV-specific CMI was quantified using interferon-gamma enzyme-linked immunosorbent spot assay, latent VZV DNA in peripheral blood mononuclear cells using ddPCR, and VZV-specific IgG using enzyme-linked immunosorbent assay. VZV-specific CMI declined significantly from age 40 (r = -0.356, p = 0.001). Latent VZV burden increased from age 50 (r = 0.459, p < 0.001). VZV-specific antibody levels showed no significant association with age (r = 0.004, p = 0.967). VZV-specific T cell responses were lower in ddPCR-positive compared with ddPCR-negative individuals (p = 0.095), although the difference was not statistically significant. VZV-specific CMI declined from age 40, while latent viral load increased from age 50. Our findings suggest that ddPCR-based quantification of latent VZV DNA may serve as a biomarker of subclinical viral reactivation, potentially informing HZ risk stratification and vaccination strategies. Further studies are required to validate the predictive value of ddPCR in identifying individuals at high risk of developing HZ.