Health Sciences North Research Institute, 41 Ramsey Lake Road, Sudbury, P3E 5J1, ON, Canada.
University of Connecticut Center on Aging, UConn Health, 263 Farmington Avenue, Farmington, 06030-5215, CT, USA.
Exp Gerontol. 2018 Jul 1;107:116-125. doi: 10.1016/j.exger.2017.09.015. Epub 2017 Sep 27.
Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in older adults may be due to a strong IL-10 response to influenza following vaccination, and persistent CMV infection.
与老年人流感疫苗效力降低相关的 T 细胞功能的年龄相关性变化。抗体和细胞介导的免疫在保护老年人方面都起着重要作用，尤其是预防流感的严重并发症。与标准剂量（SD）疫苗相比，高剂量（HD）流感疫苗可在老年人中诱导更高的抗体滴度，但对 T 细胞记忆的影响尚不清楚。本研究的目的是比较接受 HD 或 SD 流感疫苗接种的老年人的抗体和 T 细胞反应，确定巨细胞病毒（CMV）血清状态是否影响疫苗接种反应，并确定随后发生流感感染的老年人接种疫苗反应的差异。招募了（n=106）老年人（≥65 岁）并将其随机分为接受 SD 或 HD 流感疫苗接种组。接种前采集血液，然后在接种后 4、10 和 20 周采集。使用活流感病毒对 PBMC 进行体外挑战，测量血清抗体滴度以及诱导颗粒酶 B（iGrB）和细胞因子的水平。在流感季节进行的监测确定了具有实验室确诊流感疾病或感染的人。与 SD 疫苗接种相比，HD 流感疫苗接种在体外用活流感病毒挑战 PBMC 时，可诱导高抗体滴度和 IL-10 反应，以及短暂的 Th1 反应（IFN-γ 和 iGrB）增加。在感染流感的老年人中，感染后（第 10 周至 20 周）可观察到病毒挑战细胞中高 IL-10 和 iGrB 反应，以及第 20 周的 IFN-γ 和 TNF-α。此外，CMV 血清阳性的老年人对流感病毒的 iGrB 反应受损，无论疫苗剂量如何。本研究表明，HD 流感疫苗对老年人功能性 T 细胞记忆的发展几乎没有影响。此外，流感感染后老年人的不良结局可能是由于接种疫苗后对流感产生强烈的 IL-10 反应和持续的 CMV 感染。
