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成人接种 Priorix®疫苗后不同应答类型的转录组特征分析。

Transcriptomic profiling of different responder types in adults after a Priorix® vaccination.

机构信息

Department of Medical Genetics, University of Antwerp/Antwerp University Hospital, Edegem, Belgium; AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium.

AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (biomina), University of Antwerp, Antwerp, Belgium.

出版信息

Vaccine. 2020 Apr 3;38(16):3218-3226. doi: 10.1016/j.vaccine.2020.03.004. Epub 2020 Mar 9.

DOI:10.1016/j.vaccine.2020.03.004
PMID:32165045
Abstract

Thanks to the recommendation of a combined Measles/Mumps/Rubella (MMR) vaccine, like Priorix®, these childhood diseases are less common now. This is beneficial to limit the spread of these diseases and work towards their elimination. However, the measles, mumps and rubella antibody titers show a large variability in short- and long-term immunity. The recent outbreaks worldwide of measles and mumps and previous studies, which mostly focused on only one of the three virus responses, illustrate that there is a clear need for better understanding the immune responses after vaccination. Our healthy cohort was already primed with the MMR antigens in their childhood. In this study, the adult volunteers received one Priorix® vaccine dose at day 0. First, we defined 4 different groups of responders, based on their antibody titers' evolution over 4 time points (Day 0, 21, 150 and 365). This showed a high variability within and between individuals. Second, we determined transcriptome profiles using 3'mRNA sequencing at day 0, 3 and 7. Using two analytical approaches, "one response group per time point" and "a time comparison per response group", we correlated the short-term gene expression profiles to the different response groups. In general, the list of differentially expressed genes is limited, however, most of them are clearly immune-related and upregulated at day 3 and 7, compared to the baseline day 0. Depending on the specific response group there are overlapping signatures for two of the three viruses. Antibody titers and transcriptomics data showed that an additional Priorix vaccination does not facilitate an equal immune response against the 3 viruses or among different vaccine recipients.

摘要

得益于麻疹、腮腺炎、风疹(MMR)三联疫苗(如 Priorix®)的联合推荐,这些儿童疾病现在已经不那么常见了。这有利于限制这些疾病的传播,并努力消除这些疾病。然而,麻疹、腮腺炎和风疹抗体滴度在短期和长期免疫中显示出很大的可变性。最近在全球范围内爆发的麻疹和腮腺炎,以及以前的大多数研究都集中在三种病毒反应中的一种,这表明人们显然需要更好地了解疫苗接种后的免疫反应。我们的健康队列在童年时期就已经接触到了 MMR 抗原。在这项研究中,成年志愿者在第 0 天接受了一剂 Priorix®疫苗。首先,我们根据 4 个时间点(第 0、21、150 和 365 天)的抗体滴度演变,将参与者分为 4 个不同的反应者组。这表明个体内和个体间存在很大的可变性。其次,我们使用 3' mRNA 测序在第 0、3 和 7 天确定转录组谱。使用两种分析方法,“每个时间点一个反应组”和“每个反应组的时间比较”,我们将短期基因表达谱与不同的反应组相关联。一般来说,差异表达基因的数量是有限的,然而,与基线第 0 天相比,其中大多数基因明显与免疫相关,并在第 3 天和第 7 天上调。根据特定的反应组,有两个病毒的重叠特征。抗体滴度和转录组学数据表明,额外的 Priorix 疫苗接种不会促进对 3 种病毒或不同疫苗接种者的均等免疫反应。

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