{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:59:42Z","timestamp":1792058382711,"version":"4.4.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"14","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001724","name":"International Foundation for Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001724","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Immunology"],"published-print":{"date-parts":[[2008,8]]},"DOI":"10.1016\/j.molimm.2008.04.011","type":"journal-article","created":{"date-parts":[[2008,7,10]],"date-time":"2008-07-10T05:52:31Z","timestamp":1215669151000},"page":"3847-3856","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":130,"title":["VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI\u2032"],"prefix":"10.1016","volume":"45","author":[{"given":"Issam","family":"Hmila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben Abderrazek-Ben","family":"Abdallah R","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Saerens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakaria","family":"Benlasfar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Conrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed El","family":"Ayeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Muyldermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balkiss","family":"Bouhaouala-Zahar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.molimm.2008.04.011_bib1","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/S0140-6736(98)12083-4","article-title":"Serotherapy in scorpion envenomation: a randomised controlled trial","volume":"354","author":"Abroug","year":"1999","journal-title":"Lancet"},{"key":"10.1016\/j.molimm.2008.04.011_bib2","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1007\/s00134-003-1947-0","article-title":"A canine study of immunotherapy in scorpion envenomation","volume":"29","author":"Abroug","year":"2003","journal-title":"Intensive Care Med."},{"key":"10.1016\/j.molimm.2008.04.011_bib3","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s000180300053","article-title":"Design and evaluation of a diabody to improve protection against a potent scorpion neurotoxin","volume":"60","author":"Aubrey","year":"2003","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.molimm.2008.04.011_bib4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.toxicon.2003.11.024","article-title":"Engineering of a recombinant Fab from a neutralizing IgG directed against scorpion neurotoxin AahI, and functional evaluation versus other antibody fragments","volume":"43","author":"Aubrey","year":"2004","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib5","doi-asserted-by":"crossref","first-page":"214","DOI":"10.4049\/jimmunol.141.1.214","article-title":"Monoclonal antibodies to scorpion toxins. Characterization and molecular mechanisms of neutralization","volume":"141","author":"Bahraoui","year":"1988","journal-title":"J. Immunol."},{"key":"10.1016\/j.molimm.2008.04.011_bib6","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nm1395","article-title":"Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor","volume":"12","author":"Baral","year":"2006","journal-title":"Nat. Med."},{"key":"10.1016\/j.molimm.2008.04.011_bib7","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1432-1033.1996.0653w.x","article-title":"A recombinant insect-specific alpha-toxin of Buthus occitanus tunetanus scorpion confers protection against homologous mammal toxins","volume":"238","author":"Bouhaouala-Zahar","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.molimm.2008.04.011_bib8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0014-5793(99)01179-5","article-title":"Monoclonal antibodies against the Androctonus australis hector scorpion neurotoxin I: characterisation and use for venom neutralisation","volume":"458","author":"Clot-Faybesse","year":"1999","journal-title":"FEBS Lett."},{"key":"10.1016\/j.molimm.2008.04.011_bib9","doi-asserted-by":"crossref","first-page":"7346","DOI":"10.1074\/jbc.M007734200","article-title":"Camel single-domain antibodies as modular building units in bispecific and bivalent antibody constructs","volume":"276","author":"Conrath","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2008.04.011_bib10","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1128\/AAC.45.10.2807-2812.2001","article-title":"Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae","volume":"45","author":"Conrath","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.molimm.2008.04.011_bib11","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1158\/0008-5472.CAN-03-3935","article-title":"Efficient cancer therapy with a nanobody-based conjugate","volume":"64","author":"Cortez-Retamozo","year":"2004","journal-title":"Cancer Res."},{"key":"10.1016\/j.molimm.2008.04.011_bib12","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/ijc.10212","article-title":"Efficient tumor targeting by single-domain antibody fragments of camels","volume":"98","author":"Cortez-Retamozo","year":"2002","journal-title":"Int. J. Cancer."},{"key":"10.1016\/j.molimm.2008.04.011_bib13","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1073\/pnas.0505379103","article-title":"Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies","volume":"103","author":"De Genst","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.molimm.2008.04.011_bib14","doi-asserted-by":"crossref","first-page":"6729","DOI":"10.1021\/bi00020a018","article-title":"Promoter structure and intron-exon organization of a scorpion alpha-toxin gene","volume":"34","author":"Delabre","year":"1995","journal-title":"Biochemistry"},{"key":"10.1016\/j.molimm.2008.04.011_bib15","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1046\/j.1432-1327.2001.01923.x","article-title":"Construction and functional evaluation of a single-chain antibody fragment that neutralizes toxin AahI from the venom of the scorpion Androctonus australis hector","volume":"268","author":"Devaux","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.molimm.2008.04.011_bib16","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1110\/ps.34602","volume":"11","author":"Dumoulin","year":"2002","journal-title":"Protein Sci."},{"key":"10.1016\/j.molimm.2008.04.011_bib17","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/0041-0101(85)90005-4","article-title":"Polymorphism and quantitative variations of toxins in the venom of the scorpion Androctonus australis hector","volume":"23","author":"El Ayeb","year":"1985","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib18","doi-asserted-by":"crossref","first-page":"6671","DOI":"10.1021\/bi00369a052","article-title":"Use of antibodies specific to defined regions of scorpion alpha-toxin to study its interaction with its receptor site on the sodium channel","volume":"25","author":"El Ayeb","year":"1986","journal-title":"Biochemistry"},{"key":"10.1016\/j.molimm.2008.04.011_bib19","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-5793(97)01062-4","article-title":"Selection and identification of single domain antibody fragments from camel heavy-chain antibodies","volume":"414","author":"Ghahroudi","year":"1997","journal-title":"FEBS Lett."},{"key":"10.1016\/j.molimm.2008.04.011_bib20","first-page":"1655","article-title":"Is antivenom the most successful therapy in scorpion victims?","volume":"37","author":"Gueron","year":"1999","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib21","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/363446a0","article-title":"Naturally occurring antibodies devoid of light chains","volume":"363","author":"Hamers-Casterman","year":"1993","journal-title":"Nature"},{"key":"10.1016\/j.molimm.2008.04.011_bib22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.taap.2006.11.003","article-title":"Toxicokinetic and toxicodynamic analyses of Androctonus australis hector venom in rats: optimization of antivenom therapy","volume":"218","author":"Hammoudi-Triki","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.molimm.2008.04.011_bib23","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s00253-005-0300-7","article-title":"Selection and optimization of proteolytically stable llama single-domain antibody fragments for oral immunotherapy","volume":"72","author":"Harmsen","year":"2006","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.molimm.2008.04.011_bib24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00253-007-1142-2","article-title":"Properties, production, and applications of camelid single-domain antibody fragments","volume":"77","author":"Harmsen","year":"2007","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.molimm.2008.04.011_bib25","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.1093\/nar\/19.15.4133","article-title":"Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains","volume":"19","author":"Hoogenboom","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.molimm.2008.04.011_bib26","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/0041-0101(94)90384-0","article-title":"The treatment of the scorpion envenoming syndrome: the Saudi experience with serotherapy","volume":"32","author":"Ismail","year":"1994","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib27","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/S0041-0101(98)00144-5","article-title":"Pharmacokinetics of 125I-labelled IgG, F(ab\u2032)2 and Fab fractions of scorpion and snake antivenins: merits and potential for therapeutic use","volume":"36","author":"Ismail","year":"1998","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib28","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.jmb.2004.12.060","article-title":"Directed evolution, phage display and combination of evolved mutants: a strategy to recover the neutralization properties of the scFv version of BCF2 a neutralizing monoclonal antibody specific to scorpion toxin Cn2","volume":"346","author":"Ju\u00e1rez-Gonz\u00e1lez","year":"2005","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.molimm.2008.04.011_bib29","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s00018-006-6401-3","article-title":"Using a recombinant bispecific antibody to block Na+-channel toxins protects against experimental scorpion envenoming","volume":"64","author":"Juste","year":"2007","journal-title":"Cell Mol. Life Sci."},{"key":"10.1016\/j.molimm.2008.04.011_bib30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.toxicon.2004.10.007","article-title":"Pharmacokinetic studies of scorpion venom before and after antivenom immunotherapy","volume":"45","author":"Krifi","year":"2005","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib31","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0041-0101(97)00136-0","article-title":"Development of an ELISA for the detection of scorpion venoms in sera of humans envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot): correlation with clinical severity of envenoming in Tunisia","volume":"36","author":"Krifi","year":"1998","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib32","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/S0041-0101(01)00083-6","article-title":"Effects of antivenom on Buthus occitanus tunetanus (Bot) scorpion venom pharmacokinetics: towards an optimization of antivenom immunotherapy in a rabbit model","volume":"39","author":"Krifi","year":"2001","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0145-305X(02)00039-3","article-title":"IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains","volume":"27","author":"Lefranc","year":"2003","journal-title":"Dev. Comp. Immunol."},{"key":"10.1016\/j.molimm.2008.04.011_bib34","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.toxicon.2003.10.021","article-title":"Immunized camel sera and derived immunoglobulin subclasses neutralizing Androctonus australis hector scorpion toxins","volume":"42","author":"Meddeb-Mouelhi","year":"2003","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib35","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1432-1033.1970.tb01111.x","article-title":"Purification of animal neurotoxins. Isolation and characterization of eleven neurotoxins from the venoms of the scorpions Androctonus australis hector, Buthus occitanus tunetanus and Leiurus quinquestriatus quinquestriatus","volume":"16","author":"Miranda","year":"1970","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.molimm.2008.04.011_bib36","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0014-5793(98)01647-0","article-title":"A recombinant single-chain antibody fragment that neutralizes toxin II from the venom of the scorpion Androctonus australis hector","volume":"442","author":"Mousli","year":"1999","journal-title":"FEBS Lett."},{"key":"10.1016\/j.molimm.2008.04.011_bib37","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1093\/protein\/7.9.1129","article-title":"Sequence and structure of VH domain from naturally occurring camel heavy chain immunoglobulins lacking light chains","volume":"7","author":"Muyldermans","year":"1994","journal-title":"Protein Eng."},{"key":"10.1016\/j.molimm.2008.04.011_bib38","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0968-0004(01)01790-X","article-title":"Recognition of antigens by single-domain antibody fragments: the superfluous luxury of paired domains","volume":"26","author":"Muyldermans","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.molimm.2008.04.011_bib39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0065-2776(01)79006-2","article-title":"Functional heavy-chain antibodies in Camelidae","volume":"79","author":"Nguyen","year":"2001","journal-title":"Adv. Immunol."},{"key":"10.1016\/j.molimm.2008.04.011_bib40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1365-2567.2003.01633.x","article-title":"Heavy-chain only antibodies derived from dromedary are secreted and displayed by mouse B cells","volume":"109","author":"Nguyen","year":"2003","journal-title":"Immunology"},{"key":"10.1016\/j.molimm.2008.04.011_bib41","series-title":"Measuring The Conformational Stability of a Protein in Protein Structure: A Practical Approach","first-page":"299","author":"Pace","year":"1997"},{"key":"10.1016\/j.molimm.2008.04.011_bib42","first-page":"493","article-title":"A simple method of estimating fifty percent in eucariotic end point","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"10.1016\/j.molimm.2008.04.011_bib43","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/S0041-0101(98)00141-X","article-title":"Immunotherapy for scorpion envenoming in Brazil","volume":"36","author":"Rezende","year":"1998","journal-title":"Toxicon"},{"key":"10.1016\/j.molimm.2008.04.011_bib44","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/j.1432-1033.1970.tb01162.x","article-title":"The amino acid sequence of neurotoxin I of Androctonus australis hector","volume":"17","author":"Rochat","year":"1970","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.molimm.2008.04.011_bib45","doi-asserted-by":"crossref","first-page":"51965","DOI":"10.1074\/jbc.M409292200","article-title":"Single domain antibodies derived from dromedary lymph node and peripheral blood lymphocytes sensing conformational variants of prostate-specific antigen","volume":"279","author":"Saerens","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.molimm.2008.04.011_bib46","series-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook","year":"2001"},{"key":"10.1016\/j.molimm.2008.04.011_bib47","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1126\/science.3285470","article-title":"Assembly of a functional immunoglobulin Fv fragment in Escherichia coli","volume":"240","author":"Skerra","year":"1988","journal-title":"Science"},{"key":"10.1016\/j.molimm.2008.04.011_bib48","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0141-0229(01)00497-5","volume":"30","author":"Thomassen","year":"2002","journal-title":"Enzyme Microb. Technol."},{"key":"10.1016\/j.molimm.2008.04.011_bib49","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/bit.21150","article-title":"Increased heterologous protein production by Saccharomyces cerevisiae growing on ethanol as sole carbon source","volume":"96","author":"Van de Laar","year":"2007","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.molimm.2008.04.011_bib50","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0161-5890(97)00146-6","article-title":"Comparison of llama VH sequences from conventional and heavy chain antibodies","volume":"34","author":"Vu","year":"1997","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.molimm.2008.04.011_bib51","first-page":"5758","article-title":"High thermal stability is essential for tumor targeting of antibody fragments: engineering of a humanized anti-epithelial glycoprotein-2 (epithelial cell adhesion molecule) single-chain Fv fragment","volume":"59","author":"Willuda","year":"1999","journal-title":"Cancer Res."}],"container-title":["Molecular Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161589008001612?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0161589008001612?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T13:23:46Z","timestamp":1758979426000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0161589008001612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8]]},"references-count":51,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["S0161589008001612"],"URL":"https:\/\/doi.org\/10.1016\/j.molimm.2008.04.011","relation":{},"ISSN":["0161-5890"],"issn-type":[{"value":"0161-5890","type":"print"}],"subject":[],"published":{"date-parts":[[2008,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"VHH, bivalent domains and chimeric Heavy chain-only antibodies with high neutralizing efficacy for scorpion toxin AahI\u2032","name":"articletitle","label":"Article Title"},{"value":"Molecular Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.molimm.2008.04.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2008 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}