Characterization of neutralizing versus binding antibody and T cell responses to varicella-zoster virus in the elderly

Age-related immune changes increase the risk of herpes zoster (HZ) caused by varicella-zoster virus (VZV) reactivation. Understanding immune responses to VZV is crucial for reducing the burden of HZ in aging populations. Due to the limited availability of data regarding the VZV immune profiles of elderly individuals, particularly in developing countries, more comprehensive immunological investigations are warranted. A total of 213 participants aged ≥ 60 years were included in this study. VZV-neutralizing antibodies (NAb) and glycoprotein-binding antibodies (BAb) were quantified. Furthermore, VZV-specific T cell subsets and their functionality were evaluated using flow cytometry. Elderly individuals demonstrated a high VZV seropositivity rate of 98.6%, exceeding that of the younger adults. Interestingly, VZV-BAb increased, whereas the proportion of NAb decreased with age, with a significantly lower proportion in the elderly aged ≥ 70 years. The elderly showed decreased naïve T cells and accumulated VZV-specific aged T cells; central memory and effector memory CD4⁺ and CD8⁺ T cells, and terminal effector memory CD8⁺ T cells; with elevated expression of senescence and exhaustion markers, indicating functional impairment. Nonetheless, VZV-specific functional T cells; percentages of VZV-specific interferon-γ-secreting CD4⁺ and CD8⁺ T cells; were not diminished. These findings provide insights into aging VZV immune profiles, which will facilitate the development of age-specific HZ vaccination policies.