Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders

Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders
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DOI:
10.1016/j.vaccine.2018.09.001
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发表时间:
2018-10-08
期刊:
影响因子:
5.5
通讯作者:
Mortier, Geert
Mortier, Geert
中科院分区:
医学3区
文献类型:
--
作者:
Bartholomeus, Esther;De Neuter, Nicolas;Mortier, Geert

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简介:由于B型肝炎病毒广泛传播,并造成相当大的发病率和死亡率,世界卫生组织建议从婴儿期开始接种疫苗,以减少急性感染和慢性携带者。然而,目前的亚单位疫苗不是100%有效的,并且留下5-10%的受者unprotected.Methods:为了评估Engerix-B疫苗接种后的免疫应答,我们使用mRNA测序确定了第一次接种前、第3天和第7天接种后的全血早期基因表达特征,并将其与两次接种后产生的抗体滴度相关联。我们的研究结果表明,免疫相关基因的差异表达的反应者主要在第3天和非反应者主要在第7天。应答者和非应答者之间最显著的差异是疫苗接种前差异表达的基因。颗粒蛋白前体基因(GRN)在第0天在应答者中显著下调,而在非应答者中上调。结论:免疫无应答者在免疫前已表现出免疫系统的激活状态。此外,在接种疫苗后,与应答者相比,它们表现出延迟和部分免疫应答。我们的数据可能表明,基线和未触发的免疫系统可以影响B肝炎疫苗接种后的反应。(C)2018爱思唯尔有限公司版权所有。
Introduction: As the hepatitis B virus is widely spread and responsible for considerable morbidity and mortality, WHO recommends vaccination from infancy to reduce acute infection and chronic carriers. However, current subunit vaccines are not 100% efficacious and leave 5-10% of recipients unprotected.Methods: To evaluate immune responses after Engerix-B vaccination, we determined, using mRNA-sequencing, whole blood early gene expression signatures before, at day 3 and day 7 after the first dose and correlated this with the resulting antibody titer after two vaccine doses.Results: Our results indicate that immune related genes are differentially expressed in responders mostly at day 3 and in non-responders mostly at day 7. The most remarkable difference between responders and non-responders were the differentially expressed genes before vaccination. The granulin precursor gene (GRN) was significantly downregulated in responders while upregulated in non-responders at day 0. Furthermore, absolute granulocytes numbers were significantly higher in non-responders at day 0.Conclusion: The non-responders already showed an activated state of the immune system before vaccination. Furthermore, after vaccination, they exhibited a delayed and partial immune response in comparison to the responders. Our data may indicate that the baseline and untriggered immune system can influence the response upon hepatitis B vaccination. (C) 2018 Elsevier Ltd. All rights reserved.