{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T23:18:36Z","timestamp":1770419916981,"version":"3.49.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Both vaccine \u201ctake\u201d 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 \u201ctake.\u201d 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\u00a04 and day\u00a01 post-rTV\/HIV-1 vaccination, followed by a downregulation from day\u00a03 until day\u00a028 in responders. In contrast, AP-1 core and pro-inflammatory genes were upregulated on day\u00a07 in non-responders. We speculate that persistent pro-inflammatory signaling early post-rTV\/HIV-1 vaccination inhibits the nAb response.<\/jats:p>","DOI":"10.3389\/fimmu.2021.737487","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T16:58:53Z","timestamp":1634144333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Early Pro-Inflammatory Signal and T-Cell Activation Associate With Vaccine-Induced Anti-Vaccinia Protective Neutralizing Antibodies"],"prefix":"10.3389","volume":"12","author":[{"given":"Jue","family":"Hou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay N.","family":"Carpp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manxue","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunda","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/v7041726","article-title":"The Evolution of Poxvirus Vaccines","volume":"7","author":"Sanchez-Sampedro","year":"2015","journal-title":"Viruses"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02670-05","article-title":"CD127+CCR5+CD38+++ CD4+ Th1 Effector Cells are an Early Component of the Primary Immune Response to Vaccinia Virus and Precede Development of Interleukin-2+ Memory CD4+ T Cells","volume":"80","author":"Zaunders","year":"2006","journal-title":"J Virol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.09.086","article-title":"The Smallpox Vaccine Induces an Early Neutralizing IgM Response","volume":"28","author":"Moyron-Quiroz","year":"2009","journal-title":"Vaccine"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00392.x","article-title":"Immunity and Immunological Memory Following Smallpox Vaccination","volume":"211","author":"Amanna","year":"2006","journal-title":"Immunol Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.24.3295","article-title":"Response to Smallpox Vaccine in Persons Immunized in the Distant Past","volume":"289","author":"Frey","year":"2003","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1086\/513968","article-title":"Immunologic Responses to Vaccinia Vaccines Administered by Different Parenteral Routes","volume":"175","author":"McClain","year":"1997","journal-title":"J Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.07.082","article-title":"Clinical and Immunological Responses to Undiluted and Diluted Smallpox Vaccine With Vaccinia Virus of Lister Strain","volume":"24","author":"Hsieh","year":"2006","journal-title":"Vaccine"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.10.052","article-title":"Reactions to Small Pox Vaccine in Naive and Previously-Vaccinated Individuals","volume":"23","author":"Auckland","year":"2005","journal-title":"Vaccine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020534","article-title":"Clinical Responses to Undiluted and Diluted Smallpox Vaccine","volume":"346","author":"Frey","year":"2002","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/v11080708","article-title":"Genome of Alaskapox Virus, A Novel Orthopoxvirus Isolated From Alaska","volume":"11","author":"Gigante","year":"2019","journal-title":"Viruses"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.22.2127","article-title":"Smallpox as a Biological Weapon: Medical and Public Health Management. 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