Background

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.

Methods

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.

Findings

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).

Interpretation

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.

Funding

Sheba Medical Center, Israel Ministry of Health.

中文翻译：

---

BNT162b2 COVID-19 疫苗与体液免疫反应和动力学的相关性：一项针对卫生保健工作者的前瞻性、单中心、纵向队列研究

背景

在辉瑞-BioNTech BNT162b2 COVID-19 疫苗于 2020 年 12 月 19 日在以色列推出的同时，我们评估了不同年龄和性别的卫生保健工作者在每次接种疫苗后的早期抗体反应和抗体动力学。合并症。

方法

我们在 Sheba 医疗中心（以色列 Tel-Hashomer）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该中心的医护人员，他们在接受第一剂肌肉注射疫苗前抗 SARS-CoV-2 IgG 检测呈阴性，并在第一剂疫苗后至少进行了一次血清抗体检测。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 的医护人员被排除在研究之外。参与者在第一次疫苗接种后每周随访 5 周；在第 3 周给予第二剂。 在基线和每周随访时采集血清样本，并在第一剂疫苗接种后 1-2 周检测抗体，在第 3 周接种第二剂疫苗，以及在第 4-5 周（即第二剂疫苗接种后 1-2 周）。有合并症的参与者参加了一个丰富的合并症亚组，并且在这些个体的 5 周随访期间至少进行了两次中和试验。对整个研究人群进行了 IgG 检测，而 IgM、IgA 和中和抗体检测仅在富集的合并症亚组中进行。IgG 浓度大于 0·62 样本与截断值 (s/co) 之比，IgA 大于 1·1 s/co，中和抗体滴度大于 10 被认为是阳性。散点图和相关分析、逻辑和线性回归分析以及线性混合模型用于研究纵向抗体反应。

发现

在 2020 年 12 月 19 日至 2021 年 1 月 30 日期间，我们从 2607 名合格的接种疫苗的参与者那里获得了 4026 份血清样本。342 个人被包括在丰富的合并症亚组中。在第 3 周，803 名个体中的 707 名 (88·0%) 和 372 名个体中的 264 名 (71·0%) 分别在第 3 周引起了第一剂疫苗的阳性 IgG 和中和抗体反应，并在第 4 周迅速增加（即，第二次疫苗接种后 1 周）分别在 1027 人中的 1011 人（98·4%）和 370 人中的 357 人中（96·5%）。接种疫苗后超过 4 周的随访，高度相关（r=0·92) 在针对受体结合域的 IgG 和中和抗体滴度之间检测到。在 66 岁及以上的个体（均值比为 0·25，95% CI 0·19–0·31）和免疫抑制个体（0·21、0·14-0·31 ) 分别与 18·00-45·99 岁的个体和没有免疫抑制的个体进行比较。这种差异在第二次给药后部分消除。总体而言，终点回归分析表明，较低的抗体浓度始终与男性（均值比为 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）和其他特定合并症：糖尿病（0·88、0·79-0·98）、高血压（0·90、0 ·82-0·98）、心脏病（0·86、0·75-1·00）和自身免疫性疾病（0·82、

解释

BNT162b2 疫苗可诱导强大而快速的抗体反应。受体结合域 IgG 抗体与中和效价之间的显着相关性表明 IgG 抗体可能作为中和的相关物。第二剂疫苗对老年人和免疫抑制的个体尤其重要，突出了及时第二剂疫苗接种的必要性，并可能重新评估某些国家两次剂量之间的长期差距。易感人群的抗体反应降低，因此他们可能更容易发生突破性感染。

资金

以色列卫生部示巴医疗中心。