Biomarkers of Vaccine Immunosafety (BioVacSafe) - Study CRC305A

The time course of whole blood gene expression was determined in healthy adult participants residing in an inpatient unit (CRC, University of Surrey, UK) to minimise background environmental variation, who were randomised into three protocols (305A, 305B and 305C) with study groups within each protocol receiving a single immunisation with a licensed vaccine or saline placebo control. In 305A participants were randomised to receive one of the following vaccines: STAMARIL: subcutaneous live yellow fever vaccine given to yellow-fever seronegative participants; VARILRIX: subcutaneous live varicella zoster vaccine given to varicella zoster seropositive participants; PLACEBO AB1C : a control group distributed across the three protocols that received immunisation with 0.5 mL normal saline intramuscularly (protocols 305B and 305C) or subcutaneously (305A). Participants were resident in the inpatient unit between days -1 and 5. Vaccines were administered at 08:00H on day 0. For RNA sequence analysis pre-immunisation baseline samples were drawn at 08:00H on day 0, and further samples collected every 4 hours thereafter on days 0, 1 and 2 (hours 0 - 60). Times are accurate to within 15 minutes. All samples were collected into PaxGene tubes. Transcriptomics analysis from Agilent arrays have also been uploaded to GEO (GSE124533) for overlapping time points and for other days.

本研究针对居住于英国萨里大学CRC住院研究病房的健康成年受试者开展全血基因表达时间进程检测，以最大限度减少背景环境变异的影响。受试者被随机分配至3个试验方案（305A、305B及305C），每个方案内的研究组分别接受获批疫苗或生理盐水安慰剂的单次免疫接种。在305A方案中，受试者被随机接种以下疫苗之一：STAMARIL：针对黄热血清学阴性受试者的皮下注射减毒黄热疫苗；VARILRIX：针对水痘带状疱疹血清学阳性受试者的皮下注射减毒水痘带状疱疹疫苗；PLACEBO AB1C：跨三个方案设置的对照组，受试者接受0.5 mL生理盐水肌内注射（305B、305C方案）或皮下注射（305A方案）免疫。受试者于第-1天至第5天入住住院研究病房。疫苗于第0天08:00接种。针对RNA测序分析，免疫前基线样本采集于第0天08:00，随后在第0、1、2天每隔4小时采集一次后续样本（覆盖0至60小时时段），采样时间精准度控制在±15分钟以内。所有样本均采集于PaxGene采血管（PaxGene Tubes）中。另有安捷伦（Agilent）基因芯片的转录组学分析数据，针对重叠时间点及其他天数，已上传至基因表达综合数据库（Gene Expression Omnibus，GEO）的GSE124533数据集。