BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers.
BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers.
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BNT 162 b2 COVID-19疫苗与体液免疫应答和动力学的相关性：一项针对卫生保健工作者的前瞻性、单中心、纵向队列研究
DOI：
10.1016/s2213-2600(21)00220-4
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
Kreiss Y
中科院分区：
文献类型：
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作者：
Lustig Y;Sapir E;Regev-Yochay G;Cohen C;Fluss R;Olmer L;Indenbaum V;Mandelboim M;Doolman R;Amit S;Mendelson E;Ziv A;Huppert A;Rubin C;Freedman L;Kreiss Y
在2020年12月19日开始在以色列推出辉瑞- biontech BNT162b2 COVID-19疫苗的同时，我们评估了不同年龄、性别和不同合并症的卫生保健工作者每次接种疫苗后的早期抗体反应和抗体动力学。我们在Sheba医学中心（Tel-Hashomer, Israel）进行了一项前瞻性、单中心、纵向队列研究。符合条件的参与者是中心的卫生保健工作者，他们在接受第一剂肌肉注射疫苗之前抗sars - cov -2 IgG检测呈阴性，并且在第一剂疫苗后至少进行一次血清学抗体检测。排除接种前SARS-CoV-2 PCR检测阳性、接种前抗SARS-CoV-2 IgG血清学检测阳性或接种后感染COVID-19的卫生保健工作者。首次接种疫苗后，参与者每周随访5周；第3周给予第二次剂量。在基线和每周随访时采集血清样本，并在接种第一剂疫苗后1-2周、接种第二剂疫苗后第3周和接种第二剂疫苗后4-5周（即接种第二剂疫苗后1-2周）检测抗体。有合并症的参与者被纳入一个合并症丰富的亚组，在5周的随访期间，对这些个体进行了至少两次中和试验。IgG检测对整个研究人群进行，而IgM、IgA和中和抗体检测仅在合并症富集亚组中进行。IgG浓度大于0.62 s/co， IgA浓度大于1.1 s/co，中和抗体滴度大于10均为阳性。采用散点图和相关分析、logistic和线性回归分析以及线性混合模型对抗体的纵向反应进行研究。在2020年12月19日至2021年1月30日期间，我们从2607名符合条件的接种疫苗参与者中获得了4026份血清样本。342名患者被纳入合并症富集亚组。在第3周，803例中有707例（88.0%）和372例中有264例（71%）出现IgG和中和抗体阳性反应，在第4周（即第2次接种后1周），1027例中有1011例（98.4%）和370例中有357例（96.5%）出现IgG和中和抗体阳性反应。在接种疫苗后4周的随访中，检测到针对受体结合域的IgG与中和抗体滴度之间存在高相关性（r= 0.92）。66岁及以上人群（平均比值0.25,95% CI 0.19 - 0.31）和免疫抑制人群（0.21、0.14 - 0.31）首次剂量诱导的IgG应答均显著低于无免疫抑制人群（18.00 - 45.99岁）。第二次注射后，这种差异部分消失了。总体而言，终点回归分析显示，抗体浓度较低与男性（平均比值0.84,95% CI 0.80 - 0.89）、年龄较大（即≥66岁；0.64,0.58 - 0.71）、免疫抑制（0.44,0.33 - 0.58）以及其他特定合共病相关：糖尿病（0.88,0.79 - 0.98）、高血压（0.90,0.82 - 0.98）、心脏病（0.86,0.75 - 0.00）和自身免疫性疾病（0.82,0.73 - 0.92）。BNT162b2疫苗可诱导稳健、快速的抗体应答。受体结合域IgG抗体与中和效价之间的显著相关性表明，IgG抗体可能与中和作用相关。第二剂疫苗对老年人和免疫抑制个体尤其重要，这突出表明需要及时进行第二次疫苗接种，并可能重新评估一些国家剂量之间的长期差距。抗体反应在易感人群中减少，因此他们可能更容易发生突破性感染。以色列卫生部示巴医疗中心。
Concurrent with the Pfizer–BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1–2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4–5 (ie, 1–2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19–0·31) and immunosuppressed individuals (0·21, 0·14–0·31) compared with individuals aged 18·00–45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80–0·89), older age (ie, ≥66 years; 0·64, 0·58–0·71), immunosuppression (0·44, 0·33–0·58), and other specific comorbidities: diabetes (0·88, 0·79–0·98), hypertension (0·90, 0·82–0·98), heart disease (0·86, 0·75–1·00), and autoimmune diseases (0·82, 0·73–0·92). BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. Sheba Medical Center, Israel Ministry of Health.