{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:42:54Z","timestamp":1766504574910,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T00:00:00Z","timestamp":1496016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The only approved treatment for botulism relies on passive immunity which is mostly based on antibody preparations collected from hyper\u2010immune horses. The IgG Fc fragment is commonly removed from these heterologous preparations to reduce the incidence of hyper\u2010sensitivity reactions. New\u2010generation therapies entering the pipeline are based on a combination of humanized monoclonal antibodies (MAbs), which exhibit improved safety and pharmacokinetics. In the current study, a systematic and quantitative approach was applied to measure the direct contribution of homologous Fc to the potency of monoclonal and polyclonal antitoxin preparations in mice. Homologous Fc increased the potency of three individual anti\u2010botulinum toxin MAbs by up to one order of magnitude. Moreover, Fc fragment removal almost completely abolished the synergistic potency obtained from a combined preparation of these three MAbs. The MAb mixture neutralized a 400\u2010mouse median lethal dose (MsLD50) of botulinum toxin, whereas the F(ab\u2032)2 combination failed to neutralize 10 MsLD50 of botulinum toxin. Notably, increased avidity did not compensate for this phenomenon, as a polyclonal, hyper\u2010immune, homologous preparation lost 90% of its potency as well upon Fc removal. Finally, the addition of homologous Fc arms to a heterologous pharmaceutical anti\u2010botulinum toxin polyclonal horse F(ab\u2032)2 preparation improved its efficacy when administered to intoxicated symptomatic mice. Our study extends the aspects by which switching from animal\u2010based to human\u2010based antitoxins will improve not only the safety but also the potency and efficacy of passive immunity against toxins.<\/jats:p>","DOI":"10.3390\/toxins9060180","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T04:35:42Z","timestamp":1496118942000},"page":"180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of Homologous Fc Fragment in the Potency and Efficacy of Anti\u2010Botulinum Antibody Preparations"],"prefix":"10.3390","volume":"9","author":[{"given":"Amram","family":"Torgeman","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyal","family":"Ozeri","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alon","family":"Ben David","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eran","family":"Diamant","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7604-1755","authenticated-orcid":false,"given":"Osnat","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arieh","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ada","family":"Barnea","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arik","family":"Makovitzki","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avishai","family":"Mimran","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Zichel","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4161\/19420862.2015.989042","article-title":"The therapeutic monoclonal antibody market","volume":"7","author":"Ecker","year":"2015","journal-title":"mAbs"},{"key":"ref_2","first-page":"811","article-title":"FDA approves antitoxin antibody","volume":"15","author":"Mullard","year":"2016","journal-title":"Nat. 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