{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:31:51Z","timestamp":1791311511422,"version":"4.3.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"51","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,12,19]]},"abstract":"<jats:p>The proinflammatory cytokine TNF\u03b1 is a potent mediator of septic shock and a therapeutic target for chronic inflammatory pathologies including rheumatoid arthritis and Crohn's disease. As an alternative to anti-human TNF\u03b1 (hTNF\u03b1) mAbs and other hTNF\u03b1 blocker approved drugs, we developed an active anti-hTNF\u03b1 immunotherapy, based on a vaccine comprised of a keyhole limpet hemocyanin-hTNF\u03b1 heterocomplex immunogen (hTNF\u03b1 kinoid) adjuvanted in incomplete Freund's adjuvant. In mice transgenic for hTNF\u03b1 (TTg mice), hTNF\u03b1 kinoid vaccination elicited high titers of Abs that neutralized hTNF\u03b1 bioactivities but did not result in a cellular response to hTNF\u03b1. The vaccine was safe and effective in two experimental models. Kinoid-immunized but not control TTg mice resisted hTNF\u03b1-driven shock in one model and were prevented from spontaneous arthritis, inflammatory synovitis, and articular destruction in a second model. These data demonstrate an anti-cytokine induction of autoimmune protection against both acute and chronic hTNF\u03b1 exposure. They show that active vaccination against a human cytokine can be achieved, and that the immune response can be effective and safe.<\/jats:p>","DOI":"10.1073\/pnas.0604827103","type":"journal-article","created":{"date-parts":[[2006,12,8]],"date-time":"2006-12-08T20:50:05Z","timestamp":1165611005000},"page":"19442-19447","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":89,"title":["TNF\u03b1 kinoid vaccination-induced neutralizing antibodies to TNF\u03b1 protect mice from autologous TNF\u03b1-driven chronic and acute inflammation"],"prefix":"10.1073","volume":"103","author":[{"given":"H\u00e9l\u00e8ne","family":"Le Buanec","sequence":"first","affiliation":[{"name":"*Neovacs, Incorporated, Universit\u00e9 Pierre et Marie Curie, 96 Boulevard Raspail, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Delavall\u00e9e","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) ERI18, 74 Rue Marcel Cachin, 93017 Bobigny, France;"},{"name":"Universit\u00e9 de Paris 13, 93017 Bobigny, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Bessis","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) ERI18, 74 Rue Marcel Cachin, 93017 Bobigny, France;"},{"name":"Universit\u00e9 de Paris 13, 93017 Bobigny, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Paturance","sequence":"additional","affiliation":[{"name":"*Neovacs, Incorporated, Universit\u00e9 Pierre et Marie Curie, 96 Boulevard Raspail, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Bizzini","sequence":"additional","affiliation":[{"name":"*Neovacs, Incorporated, Universit\u00e9 Pierre et Marie Curie, 96 Boulevard Raspail, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gallo","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland, 725 West Lombard Street, Suite S307, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zagury","sequence":"additional","affiliation":[{"name":"*Neovacs, Incorporated, Universit\u00e9 Pierre et Marie Curie, 96 Boulevard Raspail, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christophe","family":"Boissier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) ERI18, 74 Rue Marcel Cachin, 93017 Bobigny, France;"},{"name":"Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Department of Rheumatology, Avicenne Hospital, 93009 Bobigny, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,12,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03727"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.20.9784"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/10878"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(93)90106-L"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2003.10.001"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04978.x"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar430"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90628-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90277-5"},{"key":"e_1_3_4_10_2","first-page":"2288","volume":"29","author":"den Broeder A","year":"2002","unstructured":"A den Broeder, L van de Putte, R Rau, M Schattenkirchner, P Van Riel, O Sander, C Binder, H Fenner, Y Bankmann, R Velagapudi, et al. J Rheumatol 29, 2288\u20132298 (2002).","journal-title":"J Rheumatol"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2005.05.003"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm939"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001574-200307000-00005"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04954-0"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07718-8"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2383::AID-ANR2>3.0.CO;2-D"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200405000-00014"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5860"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.01.064"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11849"},{"key":"e_1_3_4_21_2","first-page":"351","volume":"41","author":"Bizzini B","year":"1995","unstructured":"B Bizzini, A Achour Cell Mol Biol (Noisy-le-Grand) 41, 351\u2013356 (1995).","journal-title":"Cell Mol Biol (Noisy-le-Grand)"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141224798"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(03)00004-2"},{"key":"e_1_3_4_24_2","unstructured":"Neovacs (2004) PCT Patent Application WO 2004\/024189."},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6120"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.2.767"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/336070a0"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1385\/1592594050"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2005.01.005"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107482200"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/104303404772679995"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(96)00195-0"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.3.657"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1179"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200003)30:3<867::AID-IMMU867>3.0.CO;2-M"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.07.004"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535235"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0604827103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:30:29Z","timestamp":1649777429000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0604827103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,12,19]]},"references-count":38,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2006,12,19]]}},"alternative-id":["10.1073\/pnas.0604827103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0604827103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,12,19]]},"assertion":[{"value":"2006-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}