Influence of age and nature of primary infection on varicella-zoster virus-specific cell-mediated immune responses

Abstract

Background: Varicella-zoster virus (VZV)-specific cell-mediated immunity is important for protection against VZV disease. We studied the relationship between VZV cell-mediated immunity and age after varicella or VZV vaccination in healthy and human immunodeficiency virus (HIV)-infected individuals.

Methods: VZV responder cell frequency (RCF) determinations from 752 healthy and 200 HIV-infected subjects were used to identify group-specific regression curves on age.

Results: In healthy individuals with past varicella, VZV RCF peaked at 34 years of age. Similarly, VZV-RCF after varicella vaccine increased with age in subjects aged <1 to 43 years. In subjects aged 61-90 years, VZV RCF after zoster vaccine decreased with age. HIV-infected children had lower VZV RCF estimates than HIV-infected adults. In both groups, VZV RCF results were low and constant over age. Varicella vaccination of HIV-infected children with CD4 levels 20% generated VZV RCF values higher than wild-type infection and comparable to vaccine-induced responses of healthy children.

Conclusions: In immunocompetent individuals with prior varicella, VZV RCF peaked in early adulthood. Administration of varicella vaccine to HIV-infected or uninfected individuals aged >5 years generated VZV RCF values similar to those of immunocompetent individuals with immunity induced by wild-type infection. A zoster vaccine increased the VZV RCF of elderly adults aged <75 years to values higher than peak values induced by wild-type infection.

Figure 1

Reference curve of varicella-zoster virus (VZV) responder cell frequency (RCF) on age. Data were derived from 540 individuals with an antibody-confirmed history of wild-type varicella infection and without history of herpes zoster. Lines indicate the regression curve of VZV RCF on age and 95% confidence intervals.

Figure 2

Comparison of the varicella-zoster virus (VZV) responder cell frequency (RCF) on age curve of healthy individuals vaccinated against varicella with the reference curve. The data of the vaccine recipients (open triangles), derived from 27 healthy children and adults aged 1.5–43 years, vaccinated with 1 and 2 doses, respectively, of the varicella vaccine, are superimposed on the data from the reference group (closed circles) for the same age interval. The dashed line depicts the VZV RCF as a function of age in vaccine recipients, and the continuous line depicts that in the reference group. At the bottom of the graph, we show VZV RCF differences between groups and corresponding P values calculated at 5-year intervals from 5 to 30 years of age.

Figure 3

Comparison of varicella-zoster virus (VZV) responder cell frequency (RCF) as a function of age in human immunodeficiency virus (HIV)–infected children after chickenpox with the reference curve. The data derived from 88 HIV-infected children aged 1–23 years (open circles) with an antibody-confirmed history of varicella are superimposed on the data from the reference group (closed circles) for the same age interval. The dotted line depicts the VZV RCF as a function of age in HIV-infected children, and the continuous line depicts that in the reference group. At the bottom of the graph, we show VZV RCF differences between groups and corresponding P values calculated at 4-year intervals from 8 to 20 years of age.