{"doi":"10.3389/fimmu.2021.737487","title":"Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies","abstract":"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.","journal":"Frontiers in Immunology","year":2021,"id":201746,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":780675,"name":"Shuhui Wang","orcid":"0000-0002-1022-9349","position":1,"is_corresponding":false},{"id":780676,"name":"Dan Li","orcid":"0000-0003-1596-8033","position":2,"is_corresponding":false},{"id":539332,"name":"Lindsay N. Carpp","orcid":"0000-0003-0333-5925","position":3,"is_corresponding":false},{"id":391045,"name":"Tong Zhang","orcid":"0000-0002-2046-4502","position":4,"is_corresponding":false},{"id":780677,"name":"Ying Liu","orcid":"0000-0001-7084-512X","position":5,"is_corresponding":false},{"id":352207,"name":"Manxue Jia","orcid":null,"position":6,"is_corresponding":false},{"id":342259,"name":"Hong Peng","orcid":"0000-0002-3028-8872","position":7,"is_corresponding":false},{"id":106079,"name":"Chang Liu","orcid":"0009-0008-8169-4572","position":8,"is_corresponding":false},{"id":780678,"name":"Hao Wu","orcid":"0000-0001-9222-2521","position":9,"is_corresponding":false},{"id":331739,"name":"Yunda Huang","orcid":"0000-0003-1546-6172","position":10,"is_corresponding":false},{"id":780679,"name":"Yiming Shao","orcid":"0000-0003-1769-6502","position":11,"is_corresponding":false},{"id":780674,"name":"Jue Hou","orcid":"0000-0001-9913-8365","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:50:56.394488Z","pmid":"34707608","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}