Kurupati Raj K, Kossenkoff Andrew, Kannan Senthil, Haut Larissa H, Doyle Susan, Yin Xiangfan, Schmader Kenneth E, Liu Qin, Showe Louise, Ertl Hildegund C J
The Wistar Institute, Philadelphia, PA, USA.
The Wistar Institute, Philadelphia, PA, USA; Biomedical Graduate Group, University of Pennsylvania, Philadelphia, PA, USA.
Vaccine. 2017 Jun 27;35(30):3700-3708. doi: 10.1016/j.vaccine.2017.05.074. Epub 2017 Jun 2.
Antibody responses, B cell subset distribution in blood and the blood transcriptome were analyzed in younger and aged human subjects before and after vaccination with the inactivated influenza vaccine. In the aged, but not the younger, individuals we saw a clear difference in antibody titers including those at baseline depending on the time of vaccination and sample collection. Differences in baseline titers in aged individuals treated in the morning or afternoon in turn affected responsiveness to the vaccine. In both younger and aged individuals, the time of sample collection also affected relative numbers of some of the B cell subsets in blood. A global gene expression analysis with whole blood samples from the aged showed small but statistically significant differences depending on the time of sample collection. Our data do not indicate that timing of vaccination affects immune responsiveness of the aged, but rather shows that in clinical influenza vaccine trials timing of collection of samples can have a major and potentially misleading influence on study outcome. In future vaccine trials, timing of vaccination and sample collection should be recorded carefully to allow for its use as a study covariant.
在年轻和老年人类受试者接种灭活流感疫苗之前和之后，分析了抗体反应、血液中的B细胞亚群分布以及血液转录组。在老年人而非年轻人中，我们发现抗体滴度存在明显差异，包括基线滴度，这取决于疫苗接种时间和样本采集时间。老年个体在上午或下午接受治疗时基线滴度的差异反过来影响了对疫苗的反应性。在年轻和老年个体中，样本采集时间也影响了血液中一些B细胞亚群的相对数量。对老年个体全血样本进行的全基因表达分析显示，根据样本采集时间不同，存在微小但具有统计学意义的差异。我们的数据并未表明疫苗接种时间会影响老年人的免疫反应性，而是表明在临床流感疫苗试验中，样本采集时间可能会对研究结果产生重大且潜在的误导性影响。在未来的疫苗试验中，应仔细记录疫苗接种时间和样本采集时间，以便将其用作研究协变量。
