A systems vaccinology approach reveals temporal transcriptomic changes of immune responses to the yellow fever 17D vaccine

摘要

Here we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever 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; peripheral blood mononuclear cells were collected at 0 h and then at 4 h and Days 1, 2, 3, 5, 7, 14, 28, 84 and 168 post-vaccination and analyzed by transcriptional profiling and immunological assays.At 4 h post-vaccination, 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 days post-vaccination and a durable adaptive response, as assessed by transcriptional profiling. Co-expression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell and CD4⁺ T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for antibodies against another flavivirus exhibited significantly impaired dendritic cell, natural killer 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 dendritic cell activation, a robust antigen-specific T cell response, and a persistent B cell/memory B cell response.