Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age¹. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine² in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

尽管两剂 mRNA 疫苗接种可以针对 SARS-CoV-2 提供出色的保护，但有关疫苗针对 80 岁以上个体的关注变异 (VOC) 功效的信息很少¹。在这里，我们分析了老年参与者和年轻医护人员接种 BNT162b2 mRNA 疫苗^{2后的免疫反应。}在老年人中，第一剂疫苗接种后的血清中和和结合 IgG 或 IgA 的水平较低，其中 80 岁以上的参与者显着下降。来自 80 岁以上参与者的血清对 B.1.1.7（Alpha）、B.1.351（Beta）和 P.1 显示出较低的中和效力。(γ) VOC 比针对野生型病毒更有效，并且在第一次剂量后更有可能缺乏针对 VOC 的任何中和作用。然而，在第二次给药后，无论年龄如何，都可以检测到针对 VOC 的中和作用。首次给药后，老年应答者（其血清显示中和活性）中 SARS-CoV-2 刺突特异性记忆 B 细胞的频率高于无应答者。老年参与者的类别转换细胞的体细胞超突变明显减少。老年参与者中 SARS-CoV-2 刺突特异性 T 细胞产生的干扰素 γ 和白细胞介素 2 较低，并且这两种细胞因子主要由 CD4 T 细胞分泌。我们的结论是，老年人是高危人群，有必要采取具体措施来增强该人群的疫苗反应，特别是在存在令人担忧的变种的情况下。