Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria.
Nuffield Department of Medicine, University of Oxford, Oxford, UK.
J Biol Rhythms. 2023 Feb;38(1):98-108. doi: 10.1177/07487304221132355. Epub 2022 Nov 11.
Data from human and animal studies are highly suggestive of an influence of time of day of vaccine administration on host immune responses. In this population-based study, we aimed to investigate the effect of time of day of administration of a COVID-19 vector vaccine, ChAdOx1 nCoV-19 (AstraZeneca), on SARS-CoV-2 anti-spike S1 immunoglobulin (IgG) levels. Participants were 803 university employees who received their first vaccine dose in March 2021, had serology data at baseline and at 3 weeks, and were seronegative at baseline. Antibody levels were determined in binding antibody units (BAU/mL) using enzyme-linked immunosorbent assay (ELISA). Generalized additive models (GAM) and linear regression were used to evaluate the association of time of day of vaccination continuously and in hourly bins with antibody levels at 3 weeks. Participants had a mean age of 42 years (SD: 12; range: 21-74) and 60% were female. Time of day of vaccination was associated non-linearly ("reverse J-shape") with antibody levels. Morning vaccination was associated with the highest (9:00-10:00 h: mean 292.1 BAU/mL; SD: 262.1), early afternoon vaccination with the lowest (12:00-13:00 h: mean 217.3 BAU/mL; SD: 153.6), and late afternoon vaccination with intermediate (14:00-15:00 h: mean 280.7 BAU/mL; SD: 262.4) antibody levels. Antibody levels induced by 12:00-13:00 h vaccination (but not other time intervals) were significantly lower compared to 9:00-10:00 h vaccination after adjusting for potential confounders (beta coefficient = -75.8, 95% confidence interval [CI] = -131.3, -20.4). Our findings show that time of day of vaccination against SARS-CoV-2 has an impact on the magnitude of IgG antibody levels at 3 weeks. Whether this difference persists after booster vaccine doses and whether it influences the level of protection against COVID-19 needs further evaluation.
来自人体和动物研究的数据强烈提示疫苗接种时间对宿主免疫反应有影响。在这项基于人群的研究中，我们旨在研究 COVID-19 载体疫苗 ChAdOx1 nCoV-19（阿斯利康）接种时间对 SARS-CoV-2 刺突 S1 免疫球蛋白（IgG）水平的影响。参与者为 803 名大学员工，他们于 2021 年 3 月接种了第一剂疫苗，在基线和 3 周时有血清学数据，且基线时血清学阴性。使用酶联免疫吸附试验（ELISA）测定抗体水平。使用广义加性模型（GAM）和线性回归连续评估和每小时分组评估疫苗接种时间与 3 周时抗体水平的关联。参与者的平均年龄为 42 岁（SD：12；范围：21-74），60%为女性。疫苗接种时间与抗体水平呈非线性相关（“反转 J 形”）。早上接种疫苗与抗体水平最高（9:00-10:00 h：平均 292.1 BAU/mL；SD：262.1）相关，中午接种疫苗与抗体水平最低（12:00-13:00 h：平均 217.3 BAU/mL；SD：153.6）相关，下午晚些时候接种疫苗与抗体水平中等（14:00-15:00 h：平均 280.7 BAU/mL；SD：262.4）相关。调整潜在混杂因素后，与 9:00-10:00 h 接种相比，12:00-13:00 h 接种（但其他时间间隔接种没有）诱导的抗体水平显著较低（β系数=-75.8，95%置信区间[CI]=-131.3，-20.4）。我们的研究结果表明，SARS-CoV-2 疫苗接种时间对 3 周时 IgG 抗体水平的幅度有影响。这种差异在加强疫苗接种后是否持续存在，以及它是否影响对 COVID-19 的保护水平，需要进一步评估。
