Multidisciplinary study of the secondary immune response in grandparents re-exposed to chickenpox

Abstract

Re-exposure to chickenpox may boost varicella-zoster virus (VZV) immunity in the elderly. This secondary immune response is hypothesized to confer protection against herpes zoster. We longitudinally sampled 36 adults over the course of one year after re-exposure to chickenpox. The resulting 183 samples and those of 14 controls were assessed for VZV-specific T-cell immunity and antibody titres. The percentages of VZV-specific CD4+ IL-2-producing T-cells were increased in re-exposed grandparents compared to control participants up to 9 months after re-exposure. Using a longitudinal mixture modelling approach, we found that 25% and 17% of re-exposed grandparents showed a boosting of VZV-specific CD4+ IL-2-producing T-cells and VZV-specific antibodies, respectively. The antibody boosting occurred exclusively in cytomegalovirus (CMV) IgG-positive participants. CMV IgG-positive participants also had higher VZV IE62-specific CD4+ IFN-γ-producing T-cell percentages and VZV-specific antibody titres. The protective effect of re-exposure to chickenpox is likely limited, as boosting only occurred in 17-25% of the VZV re-exposed grandparents and for less than one year.

Figure 1

VZV-specific antibody titres. VZV-specific antibody titres are shown, using median and interquartile range, up to one year after re-exposure to chickenpox (T0, ≤1 week; T1, >1 week and ≤4 weeks; T2, >4 weeks and ≤7 weeks; T3, >7 weeks and ≤20 weeks; T4, >20 weeks and ≤39 weeks; T5, >39 weeks) and in control participants (CO). The numbers of samples per sample group are 24 (T0), 35 (T1), 37 (T2), 36 (T3), 33 (T4), 17 (T5) and 14 (CO). No significant differences were found.

Figure 2

T-cell responses against VZV IE62. Percentages of CD4+ and CD8+ IFN-γ-producing and CD4+ IL-2-producing T-cells against VZV IE62 are shown, using median and interquartile range, up to one year after re-exposure to chickenpox (T0, ≤1 week; T1, >1 week and ≤4 weeks; T2, >4 weeks and ≤7 weeks; T3, >7 weeks and ≤20 weeks; T4, >20 weeks and ≤39 weeks; T5, >39 weeks) and in control participants (CO). The number of samples per sample group are: for IFN-γ-producing T-cells, 23 (T0), 34 (T1), 36 (T2), 34 (T3), 32 (T4), 17 (T5), 14 (CO); for CD4+ IL-2-producing T-cells, 24 (T0), 34 (T1), 37 (T2), 35 (T3), 32 (T4), 17 (T5), 14 (CO); and for CD8+ IFN-γ-producing T-cells, 24 (T0), 35 (T1), 37 (T2), 35 (T3), 32 (T4), 15 (T5), 14 (CO). **p-value < 0.05.

Figure 3

T-cell responses against VZV IE63. Percentages of CD4+ and CD8+ IFN-γ-producing and CD4+ IL-2-producing T-cells against VZV IE63 are shown, using median and interquartile range, up to one year after re-exposure to chickenpox (T0, ≤1 week; T1, >1 week and ≤4 weeks; T2, >4 weeks and ≤7 weeks; T3, >7 weeks and ≤20 weeks; T4, >20 weeks and ≤39 weeks; T5, >39 weeks) and in control participants (CO). The number of samples per sample group are: for IFN-γ-producing T-cells, 23 (T0), 34 (T1), 37 (T2), 33 (T3), 31 (T4), 15 (T5), 14 (CO); for CD4+ IL-2-producing T-cells, 24 (T0), 35 (T1), 37 (T2), 36 (T3), 31 (T4), 15 (T5), 14 (CO); and for CD8+ IFN-γ-producing T-cells, 24 (T0), 35 (T1), 37 (T2), 36 (T3), 30 (T4), 13 (T5), 14 (CO). **p-value < 0.05; ***p-value < 0.01.

Figure 4

T-cell responses against VZV gE. Percentages of CD4+ and CD8+ IFN-γ-producing and CD4+ IL-2-producing T-cells against VZV gE are shown, using median and interquartile range, up to one year after re-exposure to chickenpox (T0, ≤1 week; T1, >1 week and ≤4 weeks; T2, >4 weeks and ≤7 weeks; T3, >7 weeks and ≤20 weeks; T4, >20 weeks and ≤39 weeks; T5, >39 weeks) and in control participants (CO). The number of samples per sample group are: for IFN-γ-producing T-cells, 23 (T0), 33 (T1), 36 (T2), 33 (T3), 30 (T4), 15 (T5), 12 (CO); for CD4+ IL-2-producing T-cells, 23 (T0), 35 (T1), 37 (T2), 34 (T3), 29 (T4), 14 (T5), 12 (CO); and for CD8+ IFN-γ-producing T-cells, 23 (T0), 35 (T1), 37 (T2), 34 (T3), 28 (T4), 13 (T5), 12 (CO). **p-value < 0.05.

Figure 5

Effect of CMV seropositivity on VZV-specific immunity. (a) VZV-specific antibody titres are shown, using median and interquartile range, up to one year after re-exposure to chickenpox (T0, ≤1 week; T1, >1 week and ≤4 weeks; T2, >4 weeks and ≤7 weeks; T3, >7 weeks and ≤20 weeks; T4, >20 weeks and ≤39 weeks; T5, >39 weeks) as a function of CMV seropositivity. (b) Percentages of CD4+ IFN-γ-producing T-cells against VZV IE62 are shown, using median and interquartile range, up to one year after re-exposure to chickenpox (T0, ≤1 week; T1, >1 week and ≤4 weeks; T2, >4 weeks and ≤7 weeks; T3, >7 weeks and ≤20 weeks; T4, >20 weeks and ≤39 weeks; T5, >39 weeks) as a function of CMV seropositivity. *p-value < 0.1; **p-value < 0.05.