背景:2019年冠状病毒病(COVID-19)疫苗接种后,老年和严重虚弱个体的细胞介导免疫的程度和持久性仍不清楚。控制免疫反应可能是预防严重COVID-19的关键;然而,目前尚不清楚疫苗接种是否诱导抗炎细胞免疫反应.为了解决这些问题,我们进行了一项为期48周的前瞻性纵向研究.总共106名感染幼稚的参与者(57名长期护理机构[LTCF]居民[中位年龄;89.0岁],28名门诊患者[中位年龄;72.0岁],和21名医护人员[中位年龄;51.0岁])提供外周血单核细胞(PBMC)样本,用于在初次接种疫苗之前评估特定的PBMC反应,初次接种疫苗后24周,加强疫苗接种后三个月。通过测量干扰素(IFN)-γ来检查对严重急性呼吸综合征冠状病毒2刺突蛋白的细胞免疫反应,肿瘤坏死因子(TNF),参与者刺突蛋白肽刺激的PBMC分泌的白介素(IL)-2,IL-4,IL-6和IL-10水平。
结果:LTCF居民表现出显著较低的IFN-γ,TNF,IL-2和IL-6水平高于初级疫苗接种后的医护人员。与医护人员相比,加强疫苗接种增加了LTCF居民的IL-2和IL-6水平,而LTCF居民的IFN-γ和TNF水平仍显着低于医护人员。IL-10水平与初次接种后的初始值没有显着差异,但在所有亚组中加强接种后均显着增加。多因素分析显示年龄与IFN-γ呈负相关,TNF,IL-2和IL-6水平,但不与IL-10水平。促炎细胞因子的水平,包括IFN-γ,TNF,IL-2和IL-6与体液免疫反应呈正相关,而IL-10水平没有。
结论:与普通人群相比,老年和严重虚弱的个体在接种COVID-19疫苗后可能表现出减少的突波特异性PBMC反应。单次加强疫苗接种可能不足以将老年和严重虚弱的个体的细胞介导的免疫增强到与普通人群相当的水平。此外,加强疫苗接种不仅可以诱导促炎细胞免疫反应,还可以诱导抗炎细胞免疫反应,可能减轻有害的炎症。
BACKGROUND: The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants.
RESULTS: LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not.
CONCLUSIONS: Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.