{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:01:34Z","timestamp":1775804494330,"version":"3.50.1"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tumor necrosis factor-\u237a (TNF\u237a) is central to the pathogenesis of autoimmune and inflammatory diseases, and monoclonal antibody-based TNF\u237a inhibitors are amongst the most used biologics worldwide. As an alternative to exogenously administered antibodies, active immunization has been explored as a TNF\u237a neutralization strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated a murine TNF\u237a (mTNF\u237a) Y87S point mutant expressed in\n                      <jats:italic>E. coli<\/jats:italic>\n                      that preserved the native trimeric structure while abrogating receptor binding. Using histidine-tag interactions, the antigen was displayed on the surface of immunogenic cobalt porphyrin-phospholipid (CoPoP) liposomes, which further attenuated TNF\u237a toxicity and enabled safe immunization. Immunization and protective efficacy were evaluated in murine models, including lipopolysaccharide\/galactosamine-induced lethal shock and collagen-induced arthritis (CIA). Parallel studies were conducted with a similarly engineered human TNF\u237a (hTNF\u237a) Y87S mutant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Liposome display of TNF\u237a elicited significantly higher levels of neutralizing antibodies following immunization. In mice, immunization improved survival in the lethal shock model and ameliorated clinical symptoms and joint inflammation in the CIA model. The Y87S mutation similarly detoxified hTNF\u237a constructs, which could also be effectively displayed on CoPoP liposomes. Immunization with hTNF\u237a induced high-titer anti-TNF\u237a IgG and serum neutralizing activity superior to other adjuvants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that CoPoP-based TNF\u237a point mutant vaccines can safely induce high levels of functional TNF\u237a-neutralizing antibodies. This strategy represents a potential low-cost alternative to current TNF-blocking biologics for the treatment of autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1801223","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:06:32Z","timestamp":1775801192000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunization with detoxified TNF\u03b1 elicits neutralizing antibodies and ameliorates inflammatory shock and autoimmune arthritis in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Wen-Ling","family":"Hsu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, State University of New York","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Synthetic Biology and Biomanufacturing, State Key Laboratory of Synthetic Biology, Tianjin University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, State University of New York","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramkumar T.","family":"Annamalai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, State University of New York","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Synthetic Biology and Biomanufacturing, State Key Laboratory of Synthetic Biology, Tianjin University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan F.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University at Buffalo, State University of New York","place":["New York, NY, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2008.02.040","article-title":"Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. 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