{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:46:46Z","timestamp":1791352006732,"version":"4.3.1"},"reference-count":37,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5540","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2001,10,5]]},"abstract":"<jats:p>\n            Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. Although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. To circumvent this, we expressed an anti-prion protein (anti-PrP) \u03bc chain in\n            <jats:italic>Prnp<\/jats:italic>\n            <jats:sup>o\/o<\/jats:sup>\n            mice. Transgenic mice developed sustained anti-PrP titers, which were not suppressed by introduction of\n            <jats:italic>Prnp<\/jats:italic>\n            <jats:sup>+<\/jats:sup>\n            alleles. Transgene expression prevented pathogenesis of prions introduced by intraperitoneal injection in the spleen and brain. Expression of endogenous PrP (PrP\n            <jats:sup>C<\/jats:sup>\n            ) in the spleen and brain was unaffected, suggesting that immunity was responsible for protection. This indicates the feasibility of immunological inhibition of prion disease in vivo.\n          <\/jats:p>","DOI":"10.1126\/science.1063093","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:40:17Z","timestamp":1027762817000},"page":"178-182","source":"Crossref","is-referenced-by-count":289,"title":["Prevention of Scrapie Pathogenesis by Transgenic Expression of Anti-Prion Protein Antibodies"],"prefix":"10.1126","volume":"294","author":[{"given":"Frank L.","family":"Heppner","sequence":"first","affiliation":[{"name":"Institute of Neuropathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Musahl","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Arrighi","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ru\u0308licke","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Animal Science,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Oesch","sequence":"additional","affiliation":[{"name":"Prionics AG, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland."},{"name":"European Molecular Biology Laboratory, Mouse Biology Programme, Via E. Ramarini 32, I-00016 Monterotondo (Rome), Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Aguzzi","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","unstructured":"www.doh.gov.uk\/cjd\/stats\/sept01.htm (Department of Health UK 2001)."},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/383685a0"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","unstructured":"M. E. Bruce et al. Nature 389 498 (1997).","DOI":"10.1038\/39057"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/35052063"},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","unstructured":"H. R. B\u00fceler et al. Nature 356 577 (1992).","DOI":"10.1038\/356577a0"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","unstructured":"S. B. Prusiner et al. Proc. Natl. Acad. Sci. U.S.A. 90 10608 (1993).","DOI":"10.1073\/pnas.90.22.10608"},{"key":"e_1_3_1_8_2","unstructured":"Supplementary Web material is available on Science Online at www.sciencemag.org\/cgi\/content\/full\/294\/5540\/178\/DC1."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","unstructured":"C. Korth et al. Nature 390 74 (1997).","DOI":"10.1038\/36337"},{"key":"e_1_3_1_10_2","unstructured":"Fluorescence-activated cell sorting (FACS) analysis: Several drops of retroorbital blood were collected in phosphate-buffered saline (PBS) 2% fetal calf serum 10 mM EDTA (pH 8) 15.3 mM NaN3. The following anti-mouse antibodies were used (all from BD Pharmingen San Diego CA): phycoerythrin (PE)- or fluorescein isothiocyanate (FITC)\u2013labeled anti-B220; PE- or FITC-labeled anti-IgMa; PE- or FITC-labeled anti-IgMb; FITC-labeled anti-IgD; PE-labeled anti-CD8; and FITC-labeled anti-CD4. Lysis of red blood cells was performed with FACS lysing solution (Becton Dickinson). Living cells were gated with a combination of forward scatter and side scatter. Data were acquired on a FACS Calibur (Becton Dickinson) with CellQuest software (Becton Dickinson); analyses were performed with Windows Multiple Document Interface (WinMDI Version 2.8; )."},{"key":"e_1_3_1_11_2","unstructured":"Enzyme-linked immunosorbent assay (ELISA): For anti-PrP REC ELISA 384-well plates were coated with 125 ng of recombinant mouse PrP 23-231 (33) in 30 \u03bcl of PBS overnight at 4\u00b0C. After three washing steps with ELISA buffer (PBS 0.1% Tween) plates were blocked with 5% bovine serum albumin (BSA) at room temperature. After washing plates were incubated for 2 hours at room temperature with 25 \u03bcl of two- or threefold serially diluted mouse serum in ELISA buffer containing 1% BSA in triplicate and probed with horseradish peroxidase\u2013conjugated rabbit anti-mouse IgG+A+M (H+L 1:1000 dilution) rabbit anti-mouse IgM (\u03bc chain\u2013specific 1:5000 dilution) or rabbit anti-mouse IgG (\u03b3 chain\u2013specific 1:5000 dilution; all from Zymed Laboratories San Francisco CA). Plates were developed with 2.2\u2032-azino-di-ethyl-benzothiazolinsulfonat and H 2 O 2 and optical density (OD) was measured at 405 nm. Titer was defined as the dilution of the OD turning point. Omission of sera omission of secondary antibody uncoated wells and dilutions of purified mAb 6H4 (Prionics Zurich Switzerland) (8) served as controls."},{"key":"e_1_3_1_12_2","unstructured":"F. L. Heppner et al. unpublished observation."},{"key":"e_1_3_1_13_2","unstructured":"Western blot analysis and NaPTA precipitation were done as described (7 14 34)."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","unstructured":"A. J. Raeber et al. Proc. Natl. Acad. Sci. U.S.A. 96 3987 (1999).","DOI":"10.1073\/pnas.96.7.3987"},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","unstructured":"H. R. B\u00fceler et al. Cell 73 1339 (1993).","DOI":"10.1016\/0092-8674(93)90360-3"},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","unstructured":"S. Adelstein et al. Science 251 1223 (1991).","DOI":"10.1126\/science.1900950"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.4.1009"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/1.4.321"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","unstructured":"F. Loder et al. J. Exp. Med. 190 75 (1999).","DOI":"10.1084\/jem.190.1.75"},{"key":"e_1_3_1_20_2","unstructured":"Prion inoculation of mice and infectivity bioassay: Infectious brain homogenate from mice infected with Rocky Mountain Laboratory scrapie prions (RML passage 5) was prepared as described (14). Mice were inoculated intraperitoneally with 26-gauge needles and 200-\u03bcl syringes with dilutions of the brain homogenate (in PBS containing 5% BSA 100-\u03bcl inoculation volume). All inoculated 6H4\u03bc mice had substantial anti-PrP REC titers. Infectivity bioassays were done as described (20 35)."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","unstructured":"M. Fischer et al. EMBO J. 15 1255 (1996).","DOI":"10.1002\/j.1460-2075.1996.tb00467.x"},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","unstructured":"A. Taraboulos et al. Proc. Natl. Acad. Sci. U.S.A. 89 7620 (1992).","DOI":"10.1073\/pnas.89.16.7620"},{"key":"e_1_3_1_23_2","unstructured":"Histoblots were done as described (21)."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.11.6292-6295.1991"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","unstructured":"M. A. Klein et al. Nature 390 687 (1997).","DOI":"10.1038\/37789"},{"key":"e_1_3_1_26_2","doi-asserted-by":"crossref","unstructured":"M. A. Klein et al. Nature Med. 4 1429 (1998).","DOI":"10.1038\/4022"},{"key":"e_1_3_1_27_2","doi-asserted-by":"crossref","unstructured":"F. Montrasio et al. Science 288 1257 (2000).","DOI":"10.1126\/science.288.5469.1257"},{"key":"e_1_3_1_28_2","doi-asserted-by":"crossref","unstructured":"M. A. Klein et al. Nature Med. 7 488 (2001).","DOI":"10.1038\/86567"},{"key":"e_1_3_1_29_2","unstructured":"Immunofluorescent analyses of spleens were done as described (26) with rat anti-mouse FDC-M1 antibody (clone 4C11; 1:300 dilution in PBS 0.15% BSA) for FDCs (36) and rabbit serum XN (26) against full-length mouse PrP REC (1:1000 dilution)."},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90436-7"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.18.6617"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.12.3193"},{"key":"e_1_3_1_33_2","doi-asserted-by":"crossref","unstructured":"R. M. Zinkernagel et al. Nature 345 68 (1990).","DOI":"10.1038\/345068a0"},{"key":"e_1_3_1_34_2","doi-asserted-by":"crossref","unstructured":"S. Hornemann et al. FEBS Lett. 413 277 (1997).","DOI":"10.1016\/S0014-5793(97)00921-6"},{"key":"e_1_3_1_35_2","doi-asserted-by":"crossref","unstructured":"J. Safar et al. Nature Med. 4 1157 (1998).","DOI":"10.1038\/2654"},{"key":"e_1_3_1_36_2","doi-asserted-by":"crossref","unstructured":"S. B. Prusiner et al. Ann. Neurol. 11 353 (1982).","DOI":"10.2307\/2067174"},{"key":"e_1_3_1_37_2","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.4049\/jimmunol.148.8.2331","volume":"148","author":"Kosco M. H.","year":"1992","unstructured":"Kosco M. H., Pflugfelder E., Gray D., J. Immunol. 148, 2331 (1992).","journal-title":"J. Immunol."},{"key":"e_1_3_1_38_2","unstructured":"We thank C. Korth for heat-inactivated 6H4 and 15B3 hybridoma cell pellets; C. Weissman M. Kosco D. Binder B. Odermatt for reagents and advice; and J. Weber E. Horvath M. Peltola and P. Schwarz for technical help. Supported by the Bundesamt f\u00fcr Bildung und Wissenschaft and by grants from the Swiss National Foundation (R.M.Z. and A.A.). F.L.H. and C.M. are fellows of the Human Frontier Science Program Organization."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1063093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:10:00Z","timestamp":1704838200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1063093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,10,5]]},"references-count":37,"journal-issue":{"issue":"5540","published-print":{"date-parts":[[2001,10,5]]}},"alternative-id":["10.1126\/science.1063093"],"URL":"https:\/\/doi.org\/10.1126\/science.1063093","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,10,5]]}}}