Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination.
Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination.
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DOI：
10.1038/s41541-022-00583-w
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发表时间：
2022-12-10
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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作者：
为检测针对流感病毒血凝素保守茎结构域的1型HA(CHA)嵌合通用流感病毒疫苗的免疫原性，进行了一期临床试验。接种佐剂灭活疫苗可诱导较高的抗茎抗体效价。我们试图确定与这种诱导相关的基因表达特征。对53名疫苗接种者的外周血进行了全血信使RNA测序。我们产生了53名志愿者的外周血液的纵向数据，在用CHAS启动和加强后的早期(第3天和第7天)和晚期(28天)时间点。差异表达基因分析显示，安慰剂组和减毒活疫苗组之间没有差异。然而，在接种灭活佐剂制剂后的第3天，发现与先天免疫反应和I型干扰素信号有关的基因上调。细胞类型去卷积分析显示，单核细胞标志物和不同亚群的树突状细胞作为最佳B细胞应答的介体显着丰富，血清中抗STEK抗体显着增加。免疫球蛋白相关基因的显著上调只有在接种具有抗茎IGVH1-69特异性诱导的佐剂疫苗(无论是作为引入物或增强剂)后才能观察到。这种方法提供了与强大的抗茎抗体反应相关的特定免疫信号，同时也有助于了解不同疫苗方案下CHA蛋白诱导的基因表达的调节。
A phase 1 clinical trial to test the immunogenicity of a chimeric group 1 HA (cHA) universal influenza virus vaccine targeting the conserved stalk domain of the hemagglutinin of influenza viruses was carried out. Vaccination with adjuvanted-inactivated vaccines induced high anti-stalk antibody titers. We sought to identify gene expression signatures that correlate with such induction. Messenger-RNA sequencing in whole blood was performed on the peripheral blood of 53 vaccinees. We generated longitudinal data on the peripheral blood of 53 volunteers, at early (days 3 and 7) and late (28 days) time points after priming and boosting with cHAs. Differentially expressed gene analysis showed no differences between placebo and live-attenuated vaccine groups. However, an upregulation of genes involved in innate immune responses and type I interferon signaling was found at day 3 after vaccination with inactivated adjuvanted formulations. Cell type deconvolution analysis revealed a significant enrichment for monocyte markers and different subsets of dendritic cells as mediators for optimal B cell responses and significant increase of anti-stalk antibodies in sera. A significant upregulation of immunoglobulin-related genes was only observed after administration of adjuvanted vaccines (either as primer or booster) with specific induction of anti-stalk IGVH1-69. This approach informed of specific immune signatures that correlate with robust anti-stalk antibody responses, while also helping to understand the regulation of gene expression induced by cHA proteins under different vaccine regimens.
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DOI：
10.1093/cid/cix468
发表时间：
2017-10-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Arriola C;Garg S;Anderson EJ;Ryan PA;George A;Zansky SM;Bennett N;Reingold A;Bargsten M;Miller L;Yousey-Hindes K;Tatham L;Bohm SR;Lynfield R;Thomas A;Lindegren ML;Schaffner W;Fry AM;Chaves SS
通讯作者：
Chaves SS
影响因子：
3.7
作者：
Hoek KL;Samir P;Howard LM;Niu X;Prasad N;Galassie A;Liu Q;Allos TM;Floyd KA;Guo Y;Shyr Y;Levy SE;Joyce S;Edwards KM;Link AJ
通讯作者：
Link AJ
影响因子：
30.3
作者：
Eisfeld AJ;Halfmann PJ;Wendler JP;Kyle JE;Burnum-Johnson KE;Peralta Z;Maemura T;Walters KB;Watanabe T;Fukuyama S;Yamashita M;Jacobs JM;Kim YM;Casey CP;Stratton KG;Webb-Robertson BM;Gritsenko MA;Monroe ME;Weitz KK;Shukla AK;Tian M;Neumann G;Reed JL;van Bakel H;Metz TO;Smith RD;Waters KM;N'jai A;Sahr F;Kawaoka Y
通讯作者：
Kawaoka Y
影响因子：
20.3
作者：
Blanchard-Rohner, Geraldine;Pulickal, Anoop S.;Pollard, Andrew J.
通讯作者：
Pollard, Andrew J.
DOI：
10.1038/s41572-018-0002-y
发表时间：
2018-06-28
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Krammer F;Smith GJD;Fouchier RAM;Peiris M;Kedzierska K;Doherty PC;Palese P;Shaw ML;Treanor J;Webster RG;García-Sastre A
通讯作者：
García-Sastre A