{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:09:04Z","timestamp":1792800544241,"version":"4.5.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The expression of endogenous retrotransposable elements, including long interspersed nuclear element 1 (LINE-1 or L1) and human endogenous retrovirus, accompanies neoplastic transformation and infection with viruses such as HIV. The ability to engender immunity safely against such self-antigens would facilitate the development of novel vaccines and immunotherapies. In this article, we address the safety and immunogenicity of vaccination with these elements. We used immunohistochemical analysis and literature precedent to identify potential off-target tissues in humans and establish their translatability in preclinical species to guide safety assessments. Immunization of mice with murine L1 open reading frame 2 induced strong CD8 T cell responses without detectable tissue damage. Similarly, immunization of rhesus macaques with human LINE-1 open reading frame 2 (96% identity with macaque), as well as simian endogenous retrovirus-K Gag and Env, induced polyfunctional T cell responses to all Ags, and Ab responses to simian endogenous retrovirus-K Env. There were no adverse safety or pathological findings related to vaccination. These studies provide the first evidence, to our knowledge, that immune responses can be induced safely against this class of self-antigens and pave the way for investigation of them as HIV- or tumor-associated targets.<\/jats:p>","DOI":"10.4049\/jimmunol.1200079","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T04:56:25Z","timestamp":1340859385000},"page":"1467-1479","source":"Crossref","is-referenced-by-count":56,"title":["Vaccination with Cancer- and HIV Infection-Associated Endogenous Retrotransposable Elements Is Safe and Immunogenic"],"prefix":"10.1093","volume":"189","author":[{"given":"Jonah B","family":"Sacha","sequence":"first","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"},{"name":"Vaccine and Gene Therapy Institute, Oregon Health & Science University , Beaverton, OR 97006"},{"name":"Division of Pathology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Vaccine Research, Worldwide R&D, Pfizer Canada , Kanata, Ontario K2K 2X3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianchun","family":"Chen","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakir H","family":"Ullah","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Goodwin","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A","family":"Simmons","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I","family":"Schenkman","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederike","family":"von Pelchrzim","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Gifford","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, San Francisco General Hospital, University of California , San Francisco, San Francisco, CA 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca A","family":"Nimityongskul","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura P","family":"Newman","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Wildeboer","sequence":"additional","affiliation":[{"name":"Drug Safety R&D and External Research Solutions, Worldwide R&D, Pfizer , Groton, CT 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B","family":"Lappin","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Hammond","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Castrovinci","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari M","family":"Piaskowski","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S","family":"Reed","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health & Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry A","family":"Beheler","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharsika","family":"Tharmanathan","sequence":"additional","affiliation":[{"name":"Vaccine Research, Worldwide R&D, Pfizer Canada , Kanata, Ontario K2K 2X3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vaccine Research, Worldwide R&D, Pfizer Canada , Kanata, Ontario K2K 2X3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Muscat-King","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Rieger","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rumpel","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, 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Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G","family":"Pierce","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusko","family":"Trajkovic","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Rakasz","sequence":"additional","affiliation":[{"name":"AIDS Vaccine Laboratory and Wisconsin National Primate Research Center, University of Wisconsin , Madison, WI 53705"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sing","family":"Rong","sequence":"additional","affiliation":[{"name":"Veterinary Medicine R&D, Pfizer Animal Health, Pfizer , Kalamazoo, MI 49001"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"McCluskie","sequence":"additional","affiliation":[{"name":"Vaccine Research, Worldwide R&D, Pfizer Canada , Kanata, Ontario K2K 2X3,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Christy","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Merson","sequence":"additional","affiliation":[{"name":"Vaccine Research and Drug Safety R&D, Worldwide R&D, Pfizer , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Brad","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F","family":"Nixon","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, San Francisco General Hospital, University of California , San Francisco, San Francisco, CA 94110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario A","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T","family":"Loudon","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M","family":"Pruimboom-Brees","sequence":"additional","affiliation":[{"name":"Vaccine Research, Drug Safety R&D, and Structural Biology, Worldwide R&D, Pfizer , Sandwich, Kent, CT13 9NJ,","place":["United 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Cancer Res."},{"key":"2025032409214908200_r4","doi-asserted-by":"crossref","first-page":"e18884","DOI":"10.1371\/journal.pone.0018884","article-title":"LINE-1 hypomethylation during primary colon cancer progression","volume":"6","author":"Sunami","year":"2011","journal-title":"PLoS ONE"},{"key":"2025032409214908200_r5","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.1200801","article-title":"Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers","volume":"331","author":"Ting","year":"2011","journal-title":"Science (New York, N.Y.)"},{"key":"2025032409214908200_r6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/01.cmr.0000215031.07941.ca","article-title":"Expression of the human endogenous retrovirus-K transmembrane envelope, Rec and Np9 proteins in melanomas and melanoma cell lines","volume":"16","author":"B\u00fcscher","year":"2006","journal-title":"Melanoma Res."},{"key":"2025032409214908200_r7","doi-asserted-by":"crossref","first-page":"9329","DOI":"10.1128\/JVI.00646-08","article-title":"Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer","volume":"82","author":"Contreras-Galindo","year":"2008","journal-title":"J. Virol."},{"key":"2025032409214908200_r8","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1128\/JVI.02115-07","article-title":"Variable transcriptional activity of endogenous retroviruses in human breast cancer","volume":"82","author":"Frank","year":"2008","journal-title":"J. Virol."},{"key":"2025032409214908200_r9","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1038\/sj.onc.1208543","article-title":"Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors","volume":"24","author":"Galli","year":"2005","journal-title":"Oncogene"},{"key":"2025032409214908200_r10","first-page":"1727","article-title":"Expression of human endogenous retrovirus K elements in germ cell and trophoblastic tumors","volume":"149","author":"Herbst","year":"1996","journal-title":"Am. J. 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