Kuijpers Yunus, Picavet H Susan J, de Rond Lia, de Zeeuw-Brouwer Mary-Lène, Rutkens Ryanne, Gijsbers Esther, Slits Irene, Engelfriet Peter, Buisman Anne-Marie, Verschuren W M Monique
Centre for Prevention, Lifestyle and Health, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3721 MA, The Netherlands.
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment (RIVM), Bilthoven, 3721 MA, The Netherlands.
Immun Ageing. 2023 Oct 25;20(1):57. doi: 10.1186/s12979-023-00382-4.
Immune responses to vaccination vary widely between individuals. The aim of this study was to identify health-related variables potentially underlying the antibody responses to SARS-CoV-2 vaccination in older persons. We recruited participants in the long-running Doetinchem Cohort Study (DCS) who underwent vaccination as part of the national COVID-19 program, and measured antibody concentrations to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N) at baseline (T0), and a month after both the first vaccination (T1), and the second vaccination (T2). Associations between the antibody concentrations and demographic variables, including age, sex, socio-economic status (SES), comorbidities (cardiovascular diseases and immune mediated diseases), various health parameters (cardiometabolic markers, inflammation markers, kidney- and lung function) and a composite measure of frailty ('frailty index', ranging from 0 to 1) were tested using multivariate models.
We included 1457 persons aged 50 to 92 years old. Of these persons 1257 were infection naïve after their primary vaccination series. The majority (N = 954) of these individuals were vaccinated with two doses of BNT162b2 (Pfizer) and their data were used for further analysis. A higher frailty index was associated with lower anti-S1 antibody responses at T1 and T2 for both men (R = -0.095, P = 0.05; R = -0.11, P = 0.02) and women (R = -0.24, P < 0.01; R = -0.15, P < 0.01). After correcting for age and sex the frailty index was also associated with the relative increase in anti-S1 IgG concentrations between the two vaccinations (β = 1.6, P < 0.01). Within the construct of frailty, history of a cardiac catheterization, diabetes, gastrointestinal disease, a cognitive speed in the lowest decile of the population distribution, and impaired lung function were associated with lower antibody responses after both vaccinations.
Components of frailty play a key role in the primary vaccination response to the BNT162b2 vaccine within an ageing population. Older persons with various comorbidities have a lowered immune response after their first vaccination, and while frail and sick older persons see a stronger increase after their second vaccination compared to healthy people, they still have a lower antibody response after their second vaccination.
个体对疫苗接种的免疫反应差异很大。本研究的目的是确定可能是老年人对SARS-CoV-2疫苗接种产生抗体反应基础的健康相关变量。我们在长期进行的多廷赫姆队列研究（DCS）中招募了参与者，这些参与者作为国家COVID-19计划的一部分接受了疫苗接种，并在基线（T0）、第一次接种后一个月（T1）和第二次接种后一个月（T2）测量了针对SARS-CoV-2刺突蛋白（S1）和核蛋白（N）的抗体浓度。使用多变量模型测试了抗体浓度与人口统计学变量之间的关联，这些变量包括年龄、性别、社会经济地位（SES）、合并症（心血管疾病和免疫介导疾病）、各种健康参数（心脏代谢标志物、炎症标志物、肾脏和肺功能）以及衰弱的综合测量指标（“衰弱指数”，范围从0到1）。
我们纳入了1457名年龄在50至92岁之间的人。在这些人中，1257人在初次接种疫苗系列后未感染过。这些个体中的大多数（N = 954）接种了两剂BNT162b2（辉瑞），其数据用于进一步分析。较高的衰弱指数与男性（R = -0.095，P = 0.05；R = -0.11，P = 0.02）和女性（R = -0.24，P < 0.01；R = -0.15，P < 0.01）在T1和T2时较低的抗S1抗体反应相关。在校正年龄和性别后，衰弱指数也与两次接种之间抗S1 IgG浓度的相对增加相关（β = 1.6，P < 0.01）。在衰弱的构成因素中，心脏导管插入术史、糖尿病、胃肠道疾病、处于人群分布最低十分位数的认知速度以及肺功能受损与两次接种后较低的抗体反应相关。
在老年人群中，衰弱因素在对BNT162b2疫苗的初次接种反应中起关键作用。患有各种合并症的老年人在首次接种后免疫反应降低，虽然体弱多病的老年人在第二次接种后与健康人相比抗体增加更强，但他们在第二次接种后抗体反应仍然较低。
