{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:14:36Z","timestamp":1792181676929,"version":"4.4.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Botulinum neurotoxins (BoNTs) are the most toxic proteins for humans and are classified as category A toxins. There are seven serotypes of BoNTs defined by the lack of cross-serotype toxin neutralization. Thus, an effective vaccine must neutralize each BoNT serotype. BoNTs are organized as dichain A-B toxins, where the N-terminal domain (light chain) is a zinc metalloprotease targeting soluble NSF attachment receptor proteins that is linked to the C-terminal domain (heavy chain [HC]) by a disulfide bond. The HC comprises a translocation domain and a C-terminal receptor binding domain (HCR). HCRs of the seven serotypes of BoNTs (hepta-HCR) were engineered for expression in<jats:italic>Escherichia coli<\/jats:italic>, and each HCR was purified from<jats:italic>E. coli<\/jats:italic>lysates. Immunization of mice with the<jats:italic>E. coli<\/jats:italic>-derived hepta-serotype HCR vaccine elicited an antibody response to each of the seven BoNT HCRs and neutralized challenge by 10,000 50% lethal doses of each of the seven BoNT serotypes. A solid-phase assay showed that the anti-hepta-serotype HCR sera inhibited the binding of HCR serotypes A and B to the ganglioside GT1b, the first step in BoNT intoxication of neurons. This is the first<jats:italic>E. coli<\/jats:italic>-derived vaccine that effectively neutralizes each of the seven BoNT serotypes.<\/jats:p>","DOI":"10.1128\/iai.01025-07","type":"journal-article","created":{"date-parts":[[2007,12,11]],"date-time":"2007-12-11T01:34:33Z","timestamp":1197336873000},"page":"1314-1318","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Subunit Vaccine against the Seven Serotypes of Botulism"],"prefix":"10.1128","volume":"76","author":[{"given":"Michael R.","family":"Baldwin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Tepp","sequence":"additional","affiliation":[{"name":"Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Przedpelski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Pier","sequence":"additional","affiliation":[{"name":"Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marite","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph T.","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.8.1059"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051926"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi602396x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6998-7005.2005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.02.013"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(00)01173-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4817-4822.1998"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid0808.010516"},{"key":"e_1_3_2_10_2","unstructured":"Laboratory registration and select agent transfer tracking system 1998"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05411"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.7.2738-2742.1995"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200305098"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123654"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"697","DOI":"10.4049\/jimmunol.90.5.697","volume":"90","year":"1963","unstructured":"Fiock, M. A., M. A. Cardella, and N. F. Gearinger. 1963. Studies on immunity to toxins of Clostridium botulinum. IX. Immunologic response of man to purified pentavalent ABCDE botulinum toxoid. J. Immunol.90:697-702.","journal-title":"J. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05387"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1998.0214"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.63.4.1214-1218.1997"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2007.tb03919.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.06.004"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5709-5715.2001"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.09.084"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.02.074"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20000"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.08.002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583500003292"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(93)90065-U"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172229899"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/prep.2000.1256"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01893-06"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(03)00019-6"},{"key":"e_1_3_2_32_2","first-page":"S48","volume":"19","year":"2004","unstructured":"Smith, L. A., M. J. Jensen, V. A. Montgomery, D. R. Brown, S. A. Ahmed, and T. J. Smith. 2004. Roads from vaccines to therapies. Mov. Disord.19(Suppl. 8):S48-S52.","journal-title":"Mov. Disord."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00046-06"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.68.325"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.06.094"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507596200"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2004.03.016"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01025-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01025-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T07:06:57Z","timestamp":1684134417000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01025-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["10.1128\/IAI.01025-07"],"URL":"https:\/\/doi.org\/10.1128\/iai.01025-07","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3]]},"assertion":[{"value":"2007-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-11-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}