T Cell Transcriptional Signatures of Influenza A/H3N2 Antibody Response to High Dose Influenza and Adjuvanted Influenza Vaccine in Older Adults.
T Cell Transcriptional Signatures of Influenza A/H3N2 Antibody Response to High Dose Influenza and Adjuvanted Influenza Vaccine in Older Adults.
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DOI：
10.3390/v14122763
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发表时间：
2022-12-11
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影响因子：
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老年人经历流感疫苗诱导的免疫力下降，患流感及其并发症的风险更高。因此，高剂量（例如，Fluzone）和佐剂化的（例如，Fluad）疫苗优先推荐给65岁及以上的人群。然而，T细胞转录活性塑造老年人对Fluzone和Fluad疫苗的体液免疫应答仍然知之甚少。我们设计了一项针对234名老年人（≥65岁）的研究，他们被随机分配接受Fluzone或Fluad疫苗，并在基线和免疫后第28天提供血液样本。我们测量了对甲型流感/H3 N2的体液免疫应答（血凝抑制/HAI抗体滴度），并在纯化的CD 4 + T细胞中进行了mRNA-Seq转录谱分析，以鉴定可能解释疫苗类型体液免疫应答差异的T细胞特征。鉴于制剂的巨大差异（较高的抗原剂量vs佐剂），我们的假设是每种疫苗在接种后引起不同的转录组学应答。因此，我们研究的主要焦点是鉴定影响两个疫苗组中抗体滴度的差异基因表达。我们的分析确定了三个在CD 4 + T细胞中差异表达的、功能相关的基因/蛋白：钙/钙调蛋白依赖性丝氨酸/苏氨酸激酶IV（CaMKIV），其调节因子TMEM 38 B/跨膜蛋白38 B，参与维持细胞内Ca 2+释放;和转录共激活因子CBP/CREB结合蛋白，作为CD 4 + T细胞中转录活性/功能的调节剂，影响疫苗类型的免疫应答差异。还鉴定了显著富集的T细胞特异性途径/生物学过程，其指出了流感疫苗接种后体液免疫中参与Th 1/Th 2细胞分化、IL-17信号传导、钙信号传导、Notch信号传导、MAPK信号传导和TRP阳离子Ca 2+通道调节的基因/蛋白质的重要性。总之，我们确定了CD 4 + T细胞中细胞活化和功能所必需的基因/蛋白质和途径，这些基因/蛋白质和途径与不同疫苗类型的流感疫苗诱导的体液免疫差异相关。这些发现为老年人实现保护性免疫提供了额外的机制视角。
Older adults experience declining influenza vaccine-induced immunity and are at higher risk of influenza and its complications. For this reason, high dose (e.g., Fluzone) and adjuvanted (e.g., Fluad) vaccines are preferentially recommended for people age 65 years and older. However, T cell transcriptional activity shaping the humoral immune responses to Fluzone and Fluad vaccines in older adults is still poorly understood. We designed a study of 234 older adults (≥65 years old) who were randomly allocated to receive Fluzone or Fluad vaccine and provided blood samples at baseline and at Day 28 after immunization. We measured the humoral immune responses (hemagglutination inhibition/HAI antibody titer) to influenza A/H3N2 and performed mRNA-Seq transcriptional profiling in purified CD4+ T cells, in order to identify T cell signatures that might explain differences in humoral immune response by vaccine type. Given the large differences in formulation (higher antigen dose vs adjuvant), our hypothesis was that each vaccine elicited a distinct transcriptomic response after vaccination. Thus, the main focus of our study was to identify the differential gene expression influencing the antibody titer in the two vaccine groups. Our analyses identified three differentially expressed, functionally linked genes/proteins in CD4+ T cells: the calcium/calmodulin dependent serine/threonine kinase IV (CaMKIV); its regulator the TMEM38B/transmembrane protein 38B, involved in maintenance of intracellular Ca2+ release; and the transcriptional coactivator CBP/CREB binding protein, as regulators of transcriptional activity/function in CD4+ T cells that impact differences in immune response by vaccine type. Significantly enriched T cell-specific pathways/biological processes were also identified that point to the importance of genes/proteins involved in Th1/Th2 cell differentiation, IL-17 signaling, calcium signaling, Notch signaling, MAPK signaling, and regulation of TRP cation Ca2+ channels in humoral immunity after influenza vaccination. In summary, we identified the genes/proteins and pathways essential for cell activation and function in CD4+ T cells that are associated with differences in influenza vaccine-induced humoral immunity by vaccine type. These findings provide an additional mechanistic perspective for achieving protective immunity in older adults.
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DOI：
10.1093/biostatistics/kxr054
发表时间：
2012-04
期刊：
Biostatistics (Oxford, England)
影响因子：
--
作者：
Hansen KD;Irizarry RA;Wu Z
通讯作者：
Wu Z
影响因子：
5.4
作者：
Kaiser, Madlen;Wiggin, Giselle R.;Macdonald, Andrew
通讯作者：
Macdonald, Andrew
影响因子：
6.4
作者：
Huy Quang Quach;Chen, Jun;Kennedy, Richard B.
通讯作者：
Kennedy, Richard B.
影响因子：
5.3
作者：
Anderson, KA;Means, AR
通讯作者：
Means, AR
影响因子：
6.2
作者：
Lapi, Francesco;Marconi, Ettore;Cricelli, Claudio
通讯作者：
Cricelli, Claudio