DataSheet_1_Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies.docx (2.51 MB)
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DataSheet_1_Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies.docx

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posted on 11.10.2021, 04:35 by Jue Hou, Shuhui Wang, Dan Li, Lindsay N. Carpp, Tong Zhang, Ying Liu, Manxue Jia, Hong Peng, Chang Liu, Hao Wu, Yunda Huang, Yiming Shao

Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced protection from smallpox. We analyzed a subset of samples from a phase 2a trial of three DNA/HIV-1 primes and a recombinant Tiantan vaccinia virus-vectored (rTV)/HIV-1 booster and found that a proportion of participants showed no anti-vaccinia nAb response to the rTV/HIV-1 booster, despite successful vaccine “take.” Using a rich transcriptomic and vaccinia-specific immunological dataset with fine kinetic sampling, we investigated the molecular mechanisms underlying nAb response. Blood transcription module analysis revealed the downregulation of the activator protein 1 (AP-1) pathway in responders, but not in non-responders, and the upregulation of T-cell activation in responders. Furthermore, transcriptional factor network reconstruction revealed the upregulation of AP-1 core genes at hour 4 and day 1 post-rTV/HIV-1 vaccination, followed by a downregulation from day 3 until day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV/HIV-1 vaccination inhibits the nAb response.

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