{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:23:27Z","timestamp":1777483407562,"version":"3.51.4"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T00:00:00Z","timestamp":1472083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Communitys Seventh Framework Program","award":["241832"],"award-info":[{"award-number":["241832"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0161446","type":"journal-article","created":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T18:16:54Z","timestamp":1472149014000},"page":"e0161446","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Development of Germline-Humanized Antibodies Neutralizing Botulinum Neurotoxin A and B"],"prefix":"10.1371","volume":"11","author":[{"given":"Sebastian","family":"Miethe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christelle","family":"Mazuet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Tierney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Rasetti-Escargueil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnaud","family":"Avril","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Frenzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Thullier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thibaut","family":"Pelat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Remi","family":"Urbain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Fontayne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea","family":"Sesardic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hust","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel Robert","family":"Popoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1086\/444507","article-title":"Botulism","volume":"41","author":"J Sobel","year":"2005","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"key":"ref2","first-page":"45","article-title":"Uptake of botulinum neurotoxin in the intestine","volume":"364","author":"Y Fujinaga","year":"2013","journal-title":"Curr Top Microbiol Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/infdis\/jit449","article-title":"A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins","volume":"209","author":"JR Barash","year":"2014","journal-title":"J Infect Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/infdis\/jit450","article-title":"Molecular characterization of a novel botulinum neurotoxin type h gene","volume":"209","author":"N Dover","year":"2014","journal-title":"J Infect Dis"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/infdis\/jiv327","article-title":"A Novel Botulinum Neurotoxin, Previously Reported as Serotype H, Has a Hybrid-Like Structure With Regions of Similarity to the Structures of Serotypes A and F and Is Neutralized With Serotype A Antitoxin","volume":"213","author":"SE Maslanka","year":"2016","journal-title":"J Infect Dis"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tox.2013.02.006","article-title":"Botulinum toxins: mechanisms of action, antinociception and clinical applications","volume":"306","author":"A Wheeler","year":"2013","journal-title":"Toxicology"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/infdis\/167.2.451","article-title":"A massive outbreak of type E botulism associated with traditional salted fish in Cairo","volume":"167","author":"JT Weber","year":"1993","journal-title":"J Infect Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/clinids\/23.2.337","article-title":"Experience with the use of an investigational F(ab\u2019)2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt","volume":"23","author":"RG Hibbs","year":"1996","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"key":"ref9","first-page":"20034","article-title":"Two cases of food-borne botulism in Finland caused by conserved olives, October 2011","volume":"16","author":"K Jalava","year":"2011","journal-title":"Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull"},{"key":"ref10","first-page":"20035","article-title":"Two outbreaks of botulism associated with consumption of green olive paste, France, September 2011","volume":"16","author":"JM Pingeon","year":"2011","journal-title":"Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/1471-2180-14-192","article-title":"Distinguishing highly-related outbreak-associated Clostridium botulinum type A(B) strains","volume":"14","author":"BH Raphael","year":"2014","journal-title":"BMC Microbiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1212\/01.wnl.0000187127.92446.4c","article-title":"Adult botulism type F in the United States, 1981\u20132002","volume":"65","author":"A Gupta","year":"2005","journal-title":"Neurology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins affecting neuroexocytosis","volume":"80","author":"G Schiavo","year":"2000","journal-title":"Physiol Rev"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","article-title":"Botulinum toxin as a biological weapon: medical and public health management","volume":"285","author":"SS Arnon","year":"2001","journal-title":"JAMA"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"517","DOI":"10.4161\/mabs.3.6.17621","article-title":"Antibodies for biodefense","volume":"3","author":"JW Froude","year":"2011","journal-title":"mAbs"},{"key":"ref16","unstructured":"Bozheyeva G, Kunakbayev Y, Yeleukenov D. Former Soviet Biological Weapons Facilities in Kazakhstan: Past, Present, and Future. Montrerey Inst Int Stud. 1999;Occasional Paper No. 1."},{"key":"ref17","unstructured":"Broad WJ. SOWING DEATH: A special report.; How Japan Germ Terror Alerted World. The New York Times. 26 May 1998. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.nytimes.com\/1998\/05\/26\/world\/sowing-death-a-special-report-how-japan-germ-terror-alerted-world.html\" xlink:type=\"simple\">http:\/\/www.nytimes.com\/1998\/05\/26\/world\/sowing-death-a-special-report-how-japan-germ-terror-alerted-world.html<\/ext-link>. Accessed 22 Sep 2014."},{"key":"ref18","doi-asserted-by":"crossref","first-page":"9984","DOI":"10.1073\/pnas.0408526102","article-title":"Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk","volume":"102","author":"LM Wein","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref19","first-page":"299","article-title":"Investigational heptavalent botulinum antitoxin (HBAT) to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E","volume":"59","year":"2010","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0002-9343(80)90469-6","article-title":"Hypersensitivity reactions associated with botulinal antitoxin","volume":"69","author":"RE Black","year":"1980","journal-title":"Am J Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/01.inf.0000256442.06231.17","article-title":"Infant botulism and treatment with BIG-IV (BabyBIG)","volume":"26","author":"SS Long","year":"2007","journal-title":"Pediatr Infect Dis J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1056\/NEJMoa051926","article-title":"Human botulism immune globulin for the treatment of infant botulism","volume":"354","author":"SS Arnon","year":"2006","journal-title":"N Engl J Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1080\/19420862.2015.1082016","article-title":"Development of human-like scFv-Fc antibodies neutralizing Botulinum toxin serotype B","volume":"7","author":"C Rasetti-Escargueil","year":"2015","journal-title":"mAbs"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"446","DOI":"10.4161\/mabs.27773","article-title":"Development of neutralizing scFv-Fc against botulinum neurotoxin A light chain from a macaque immune library","volume":"6","author":"S Miethe","year":"2014","journal-title":"mAbs"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12896-015-0206-0","article-title":"Isolation of nanomolar scFvs of non-human primate origin, cross-neutralizing botulinum neurotoxins A1 and A2 by targeting their heavy chain","volume":"15","author":"A Avril","year":"2015","journal-title":"BMC Biotechnol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/mab.2013.0080","article-title":"Antibody humanization methods for development of therapeutic applications","volume":"33","author":"V Ahmadzadeh","year":"2014","journal-title":"Monoclon Antibodies Immunodiagn Immunother"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4161\/mabs.1.4.8635","article-title":"Non-human primate immune libraries combined with germline humanization: an (almost) new, and powerful approach for the isolation of therapeutic antibodies","volume":"1","author":"T Pelat","year":"2009","journal-title":"mAbs"},{"key":"ref28","first-page":"1119","article-title":"\u201cSuperhumanized\u201d antibodies: reduction of immunogenic potential by complementarity-determining region grafting with human germline sequences: application to an anti-CD28","volume":"169","author":"P Tan","year":"2002","journal-title":"J Immunol Baltim Md 1950"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S1074-7613(00)00040-6","article-title":"The contribution of somatic hypermutation to the diversity of serum immunoglobulin: dramatic increase with age","volume":"13","author":"GT Williams","year":"2000","journal-title":"Immunity"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.jmb.2008.10.033","article-title":"Germline humanization of a non-human primate antibody that neutralizes the anthrax toxin, by in vitro and in silico engineering","volume":"384","author":"T Pelat","year":"2008","journal-title":"J Mol Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/pro.312","article-title":"Germline humanization of a murine Abeta antibody and crystal structure of the humanized recombinant Fab fragment","volume":"19","author":"R Robert","year":"2010","journal-title":"Protein Sci Publ Protein Soc"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/jmr.647","article-title":"IMGT standardized criteria for statistical analysis of immunoglobulin V-REGION amino acid properties","volume":"17","author":"C Pommi\u00e9","year":"2004","journal-title":"J Mol Recognit JMR"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/protein\/13.12.819","article-title":"WAM: an improved algorithm for modelling antibodies on the WEB","volume":"13","author":"NR Whitelegg","year":"2000","journal-title":"Protein Eng"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0091-6749(03)01861-X","article-title":"Allergic asthma and an anti-CD23 mAb (IDEC-152): results of a phase I, single-dose, dose-escalating clinical trial","volume":"112","author":"LJ Rosenwasser","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1158\/1078-0432.CCR-06-1463","article-title":"Phase 1 Study of Lumiliximab with Detailed Pharmacokinetic and Pharmacodynamic Measurements in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"13","author":"JC Byrd","year":"2007","journal-title":"Clin Cancer Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jbiotec.2010.09.945","article-title":"A human scFv antibody generation pipeline for proteome research","volume":"152","author":"M Hust","year":"2011","journal-title":"J Biotechnol"},{"key":"ref37","first-page":"1119","article-title":"\u201cSuperhumanized\u201d antibodies: reduction of immunogenic potential by complementarity-determining region grafting with human germline sequences: application to an anti-CD28","volume":"169","author":"P Tan","year":"2002","journal-title":"J Immunol Baltim Md 1950"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.toxicon.2006.05.007","article-title":"Botulinum type A toxin neutralisation by specific IgG and its fragments: a comparison of mouse systemic toxicity and local flaccid paralysis assays","volume":"48","author":"RGA Jones","year":"2006","journal-title":"Toxicon Off J Int Soc Toxinology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"11346","DOI":"10.1073\/pnas.172229899","article-title":"Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody","volume":"99","author":"A Nowakowski","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1128\/IAI.00405-09","article-title":"Antibody protection against botulinum neurotoxin intoxication in mice","volume":"77","author":"LW Cheng","year":"2009","journal-title":"Infect Immun"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e3023","DOI":"10.1371\/journal.pone.0003023","article-title":"Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain","volume":"3","author":"SP Adekar","year":"2008","journal-title":"PloS One"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"e12416","DOI":"10.1371\/journal.pone.0012416","article-title":"Characterization of botulinum neurotoxin type A neutralizing monoclonal antibodies and influence of their half-lives on therapeutic activity","volume":"5","author":"C Mazuet","year":"2010","journal-title":"PloS One"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e13245","DOI":"10.1371\/journal.pone.0013245","article-title":"Production and characterisation of a neutralising chimeric antibody against botulinum neurotoxin A","volume":"5","author":"J Prigent","year":"2010","journal-title":"PloS One"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"e0139905","DOI":"10.1371\/journal.pone.0139905","article-title":"Development of Human-Like scFv-Fc Neutralizing Botulinum Neurotoxin E","volume":"10","author":"S Miethe","year":"2015","journal-title":"PloS One"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1472-6750-13-52","article-title":"High level transient production of recombinant antibodies and antibody fusion proteins in HEK293 cells","volume":"13","author":"V J\u00e4ger","year":"2013","journal-title":"BMC Biotechnol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.imlet.2006.05.009","article-title":"Molecular aspects of human FcgammaR interactions with IgG: functional and therapeutic consequences","volume":"106","author":"S Sib\u00e9ril","year":"2006","journal-title":"Immunol Lett"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1128\/AEM.40.3.533-538.1980","article-title":"Limulus amoebocyte lysate assay for detection and quantitation of endotoxin in a small-volume parenteral product","volume":"40","author":"K Tsuji","year":"1980","journal-title":"Appl Environ Microbiol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/elps.1150160198","article-title":"On the separation mechanism of capillary sodium dodecyl sulfate-gel electrophoresis of proteins","volume":"16","author":"A Guttman","year":"1995","journal-title":"Electrophoresis"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"5329","DOI":"10.1021\/ac2007587","article-title":"Rapid high-resolution characterization of functionally important monoclonal antibody N-glycans by capillary electrophoresis","volume":"83","author":"Z Szabo","year":"2011","journal-title":"Anal Chem"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jmb.2005.06.003","article-title":"Molecular evolution of antibody affinity for sensitive detection of botulinum neurotoxin type A","volume":"351","author":"A Razai","year":"2005","journal-title":"J Mol Biol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/S0968-0004(96)20025-8","article-title":"Kinetic analysis of biosensor data: elementary tests for self-consistency","volume":"21","author":"P Schuck","year":"1996","journal-title":"Trends Biochem Sci"},{"issue":"Suppl 8","key":"ref53","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1002\/mds.20021","article-title":"Detection of antibodies against botulinum toxins","volume":"19","author":"D Sesardic","year":"2004","journal-title":"Mov Disord Off J Mov Disord Soc"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1007\/s00216-015-8707-1","article-title":"Characterization of botulinum neurotoxin type A subtypes by immunocapture enrichment and liquid chromatography-tandem mass spectrometry","volume":"407","author":"V Morineaux","year":"2015","journal-title":"Anal Bioanal Chem"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0161446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T14:32:21Z","timestamp":1601044341000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0161446"}},"subtitle":[],"editor":[{"given":"Jinny L","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,8,25]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0161446","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,25]]}}}