AUTHOR=Hou Jue , Wang Shuhui , Li Dan , Carpp Lindsay N. , Zhang Tong , Liu Ying , Jia Manxue , Peng Hong , Liu Chang , Wu Hao , Huang Yunda , Shao Yiming 

TITLE=Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.737487

DOI=10.3389/fimmu.2021.737487

ISSN=1664-3224

ABSTRACT=Both vaccine “take” and neutralizing antibody (nAb) titer are historical correlates for vaccine-induced smallpox protection. 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 boost and found that a proportion of participants showed no anti-vaccinia neutralizing antibody (nAb) response to the rTV/HIV-1 boost, 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 downregulation of the AP-1 pathway in responders but not non-responders, as well as upregulation of T cell-activation in responders. Furthermore, transcriptional factor network reconstruction revealed upregulation of AP-1 core genes at Hour 4 and Day 1 post rTV/HIV-1 vaccination followed by downregulation from Day 3 until Day 28 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated at Day 7 in non-responders. We speculate that persistent pro-inflammatory signaling early post rTV/HIV-1 vaccination inhibits the nAb response.