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In this study, a highly efficient expression system for the protein was developed in\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            , which provided yields that were 1 order of magnitude higher than those reported to date (350 mg H\n            <jats:sub>C<\/jats:sub>\n            per liter). The product was highly immunogenic, protecting mice from a challenge with 10\n            <jats:sup>5<\/jats:sup>\n            50% lethal dose (LD\n            <jats:sub>50<\/jats:sub>\n            ) after a single vaccination and generating a neutralizing titer of 49.98 IU\/ml after three immunizations. In addition, a single boost with H\n            <jats:sub>C<\/jats:sub>\n            increased neutralizing titers by up to 1 order of magnitude in rabbits hyperimmunized against toxoid. Moreover, we demonstrate here for the first time\n            <jats:italic>in vivo<\/jats:italic>\n            inhibition of BoNT\/A intoxication by H\n            <jats:sub>C<\/jats:sub>\n            \/A, presumably due to a blockade of the neurotoxin protein receptor SV2. Administration of H\n            <jats:sub>C<\/jats:sub>\n            \/A delayed the time to death from 10.4 to 27.3 h in mice exposed to a lethal dose of BoNT\/A (\n            <jats:italic>P<\/jats:italic>\n            = 0.0005). Since BoNT\/A and BoNT\/E partially share SV2 isoforms as their protein receptors, the ability of H\n            <jats:sub>C<\/jats:sub>\n            \/A to cross-inhibit BoNT\/E intoxication was evaluated. The administration of H\n            <jats:sub>C<\/jats:sub>\n            \/A together with BoNT\/E led to 50% survival and significantly delayed the time to death for the nonsurviving mice (\n            <jats:italic>P<\/jats:italic>\n            = 0.003). Furthermore, a combination of H\n            <jats:sub>C<\/jats:sub>\n            \/A and a subprotective dose of antitoxin E fully protected mice against 850 mouse LD\n            <jats:sub>50<\/jats:sub>\n            of BoNT\/E, suggesting complementary mechanisms of protection consisting of toxin neutralization by antibodies and receptor blocking by H\n            <jats:sub>C<\/jats:sub>\n            \/A.\n          <\/jats:p>","DOI":"10.1128\/cvi.00268-13","type":"journal-article","created":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T03:53:06Z","timestamp":1371095586000},"page":"1266-1273","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["The Receptor Binding Domain of Botulinum Neurotoxin Serotype A (BoNT\/A) Inhibits BoNT\/A and BoNT\/E Intoxications\n            <i>In Vivo<\/i>"],"prefix":"10.1128","volume":"20","author":[{"given":"Alon","family":"Ben David","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eran","family":"Diamant","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ada","family":"Barnea","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osnat","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amram","family":"Torgeman","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Zichel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.46.1.86-94.1982"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"794","DOI":"10.4161\/hv.9420","article-title":"Botulinum neurotoxin vaccines: past history and recent developments","volume":"5","author":"Rusnak JM","year":"2009","unstructured":"RusnakJM SmithLA. 2009. 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