A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune Responses to the Yellow Fever 17D Vaccine

• Published in: The Journal of immunology (1950) Vol. 199; no. 4; pp. 1476 - 1489
• Main Authors: Hou, Jue, Wang, Shuhui, Jia, Manxue, Li, Dan, Liu, Ying, Li, Zhengpeng, Zhu, Hong, Xu, Huifang, Sun, Meiping, Lu, Li, Zhou, Zhinan, Peng, Hong, Zhang, Qichen, Fu, Shihong, Liang, Guodong, Yao, Lena, Yu, Xuesong, Carpp, Lindsay N, Huang, Yunda, McElrath, Julie, Self, Steve, Shao, Yiming
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15.08.2017
• Subjects: Adaptive Immunity - genetics; Adult; Antibodies, Viral - blood; B-Lymphocytes - immunology; CC chemokine receptors; CCR1 protein; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cohort Studies; Cytokines - genetics; Cytokines - immunology; Dendritic cells; Dendritic Cells - immunology; Desmoplakins - genetics; Desmoplakins - immunology; Female; gamma Catenin; Gene Expression Profiling; Gene Expression Regulation; Humans; Immune response; Immunity, Innate - genetics; Immunologic Memory; Immunological memory; Innate immunity; Leukocytes, Mononuclear - immunology; Lymphocyte Activation; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Natural killer cells; Stat1 protein; Systems Biology - methods; T cell receptors; Transcription factors; Vaccination; Vaccines; Yellow fever; Yellow Fever - prevention & control; Yellow Fever Vaccine - administration & dosage; Yellow Fever Vaccine - immunology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1700083

In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4+ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response.