Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
Front Immunol. 2018 Jan 23;9:46. doi: 10.3389/fimmu.2018.00046. eCollection 2018.
Prevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV).
Blood samples were taken pre-, 14 days, 28 days, and 1 year after a primary VZV vaccination (Zostavax) at middle age ( = 53, 50-65 years of age). VZV-specific IFNγ-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis.
Robust short-term enhancement of the VZV-specific IFNγ-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFNγ-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFNγ-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to "exhausted" VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFNγ-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFNγ-producing cells.
These results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFNγ-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to strengthen immunity before reaching old age.
在人口快速老龄化的背景下，预防传染病至关重要。然而，老年人的疫苗反应往往会减弱。及时为中年成年人接种疫苗可能会改善疫苗的免疫反应，尽管目前对中年成年人的病原体特异性免疫反应和影响这些反应的因素知之甚少。因此，我们研究了接种活减毒水痘带状疱疹病毒（VZV）疫苗佐剂（Zostavax）后的免疫反应。
在中年（ = 53 岁，50-65 岁）时，在初次 VZV 疫苗（Zostavax）接种前、接种后 14 天、28 天和 1 年采集血样。通过 ELISpot 测量 VZV 特异性 IFNγ 产生细胞，通过流式细胞术测量激活的 T 细胞，通过荧光珠基于多重免疫分析测量抗体水平和细胞因子反应，并通过 TruCOUNT 分析测量全血细胞动力学。
在中年成年人中，接种后观察到 VZV 特异性 IFNγ 产生细胞数量的短期显著增强。值得注意的是，仅在 VZV 特异性预接种 IFNγ 产生细胞数量较少的参与者中诱导了 VZV 特异性 IFNγ 产生细胞数量的长期增强，这些参与者年龄明显较大。与 VZV 特异性预接种 IFNγ 产生细胞数量较高的参与者中“耗尽”的 VZV 特异性 CD8 T 细胞相反，这些参与者还表现出 VZV 特异性激活的 CD4 T 细胞的增强。最后，高 CD4/CD8 T 细胞比值与 VZV 特异性预接种 IFNγ 产生细胞数量较低相关。
这些结果表明，在 60 岁出头的成年人中，CD4/CD8 T 细胞比值较高且 VZV 特异性 IFNγ 产生细胞数量较低的成年人受益于 VZV 疫苗接种。这为了解影响中年成年人 VZV 特异性免疫反应的因素以及在达到老年之前增强免疫力的策略提供了重要知识。
