Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
Department of Medicine, University of Cambridge, Cambridge, UK.
Nature. 2021 Aug;596(7872):417-422. doi: 10.1038/s41586-021-03739-1. Epub 2021 Jun 30.
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 age. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine 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.
虽然两剂 mRNA 疫苗为预防 SARS-CoV-2 提供了极好的保护,但对于 80 岁以上人群中针对关注变异株(VOC)的疫苗效力知之甚少。在此,我们分析了接受 BNT162b2 mRNA 疫苗接种的老年参与者和年轻医护人员的免疫反应。与年轻参与者相比,老年人在接种第一针后血清中和抗体以及结合 IgG 或 IgA 水平较低,而 80 岁以上的参与者下降更为明显。80 岁以上参与者的血清对 B.1.1.7(Alpha)、B.1.351(Beta)和 P.1.(Gamma)VOC 的中和效力低于对野生型病毒的中和效力,且在接种第一针后更有可能对 VOC 缺乏任何中和作用。然而,在接种第二针后,无论年龄大小,均可检测到对 VOC 的中和作用。与非应答者相比,在第一针后,老年应答者(其血清显示具有中和活性)的 SARS-CoV-2 刺突特异性记忆 B 细胞的频率更高。与年轻参与者相比,老年参与者的同种型转换细胞的体细胞高频突变明显减少。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水平较低,且这两种细胞因子主要由 CD4 T 细胞分泌。我们的结论是,老年人是高风险人群,需要采取特别措施来增强该人群的疫苗反应,特别是在关注的变异株流行时。