A bispecific nanobody to provide full protection against lethal scorpion envenoming.
Identifieur interne : 000103 ( Main/Exploration ); précédent : 000102; suivant : 000104A bispecific nanobody to provide full protection against lethal scorpion envenoming.
Auteurs : Issam Hmila [Tunisie] ; Dirk Saerens ; Rahma Ben Abderrazek ; Cécile Vincke ; Naima Abidi ; Zakaria Benlasfar ; Jochen Govaert ; Mohamed El Ayeb ; Balkiss Bouhaouala-Zahar ; Serge MuyldermansSource :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2010.
Descripteurs français
- KwdFr :
- MESH :
- immunologie : Fragments d'immunoglobuline, Venins de scorpion.
- isolement et purification : Fragments d'immunoglobuline.
- Animaux, Cartographie épitopique, Chameaux, Mâle, Souris.
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : Immunoglobulin Fragments, Scorpion Venoms.
- chemical , isolation & purification : Immunoglobulin Fragments.
- Animals, Camelus, Epitope Mapping, Male, Mice.
Abstract
Envenoming following scorpion sting is a common emergency in many parts of the world. Our aim was to ameliorate the current 100-kDa horse plasma antivenom serum (PAS)-derived Fab'(2) to more quickly reach the highly diffusible scorpion toxins (7 kDa). We immunized dromedaries with toxins from Androctonus australis hector (Aah) scorpions and cloned the single-domain antibody fragments or nanobodies (15 kDa) from their B cells. Nanobodies against AahI' toxin (with AahII the most toxic compound of the venom) were retrieved from the libraries, and their AahI'-toxin neutralization was monitored in mice. Remarkably, the NbAahI'F12 fully protected mice against 100 LD(50) of AahI' administered intracerebroventricularly. Moreover, where PAS failed completely to neutralize 2 LD(50) of crude venom injected subcutaneously, the designed bispecific NbF12-10 against AahI'/AahII toxins succeeded in neutralizing 5 LD(50). Finally, in a challenge assay in which mice were subcutaneously injected with a lethal dose of scorpion venom, the subsequent intravenous injection of 85 microg of NbF12-10 protected all mice, even if the whole procedure was repeated 3 times. Furthermore, the NbF12-10 remained fully protective when mice with severe signs of envenoming were treated a few minutes before the untreated mice died.
DOI: 10.1096/fj.09-148213
PubMed: 20410443
Affiliations:
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- to stream PubMed, to step Curation: 000711
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Le document en format XML
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Pasteur, BP-74, 1002 Tunis, Tunisia.</nlm:affiliation><country xml:lang="fr">Tunisie</country><wicri:regionArea>Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Pl. Pasteur, BP-74, 1002 Tunis</wicri:regionArea><placeName><settlement type="city">Tunis</settlement><region nuts="2">Gouvernorat de Tunis</region></placeName></affiliation></author><author><name sortKey="Saerens, Dirk" sort="Saerens, Dirk" uniqKey="Saerens D" first="Dirk" last="Saerens">Dirk Saerens</name></author><author><name sortKey="Ben Abderrazek, Rahma" sort="Ben Abderrazek, Rahma" uniqKey="Ben Abderrazek R" first="Rahma" last="Ben Abderrazek">Rahma Ben Abderrazek</name></author><author><name sortKey="Vincke, Cecile" sort="Vincke, Cecile" uniqKey="Vincke C" first="Cécile" last="Vincke">Cécile Vincke</name></author><author><name sortKey="Abidi, Naima" sort="Abidi, Naima" uniqKey="Abidi N" first="Naima" last="Abidi">Naima Abidi</name></author><author><name sortKey="Benlasfar, Zakaria" sort="Benlasfar, Zakaria" uniqKey="Benlasfar Z" first="Zakaria" last="Benlasfar">Zakaria Benlasfar</name></author><author><name sortKey="Govaert, Jochen" sort="Govaert, Jochen" uniqKey="Govaert J" first="Jochen" last="Govaert">Jochen Govaert</name></author><author><name sortKey="El Ayeb, Mohamed" sort="El Ayeb, Mohamed" uniqKey="El Ayeb M" first="Mohamed" last="El Ayeb">Mohamed El Ayeb</name></author><author><name sortKey="Bouhaouala Zahar, Balkiss" sort="Bouhaouala Zahar, Balkiss" uniqKey="Bouhaouala Zahar B" first="Balkiss" last="Bouhaouala-Zahar">Balkiss Bouhaouala-Zahar</name></author><author><name sortKey="Muyldermans, Serge" sort="Muyldermans, Serge" uniqKey="Muyldermans S" first="Serge" last="Muyldermans">Serge Muyldermans</name></author></analytic><series><title level="j">FASEB journal : official publication of the Federation of American Societies for Experimental Biology</title><idno type="eISSN">1530-6860</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Camelus (MeSH)</term><term>Epitope Mapping (MeSH)</term><term>Immunoglobulin Fragments (immunology)</term><term>Immunoglobulin Fragments (isolation & purification)</term><term>Male (MeSH)</term><term>Mice (MeSH)</term><term>Scorpion Venoms (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cartographie épitopique (MeSH)</term><term>Chameaux (MeSH)</term><term>Fragments d'immunoglobuline (immunologie)</term><term>Fragments d'immunoglobuline (isolement et purification)</term><term>Mâle (MeSH)</term><term>Souris (MeSH)</term><term>Venins de scorpion (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Immunoglobulin Fragments</term><term>Scorpion Venoms</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Immunoglobulin Fragments</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Fragments d'immunoglobuline</term><term>Venins de scorpion</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Fragments d'immunoglobuline</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Epitope Mapping</term><term>Male</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cartographie épitopique</term><term>Chameaux</term><term>Mâle</term><term>Souris</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Envenoming following scorpion sting is a common emergency in many parts of the world. Our aim was to ameliorate the current 100-kDa horse plasma antivenom serum (PAS)-derived Fab'(2) to more quickly reach the highly diffusible scorpion toxins (7 kDa). We immunized dromedaries with toxins from Androctonus australis hector (Aah) scorpions and cloned the single-domain antibody fragments or nanobodies (15 kDa) from their B cells. Nanobodies against AahI' toxin (with AahII the most toxic compound of the venom) were retrieved from the libraries, and their AahI'-toxin neutralization was monitored in mice. Remarkably, the NbAahI'F12 fully protected mice against 100 LD(50) of AahI' administered intracerebroventricularly. Moreover, where PAS failed completely to neutralize 2 LD(50) of crude venom injected subcutaneously, the designed bispecific NbF12-10 against AahI'/AahII toxins succeeded in neutralizing 5 LD(50). Finally, in a challenge assay in which mice were subcutaneously injected with a lethal dose of scorpion venom, the subsequent intravenous injection of 85 microg of NbF12-10 protected all mice, even if the whole procedure was repeated 3 times. Furthermore, the NbF12-10 remained fully protective when mice with severe signs of envenoming were treated a few minutes before the untreated mice died.</div></front></TEI><affiliations><list><country><li>Tunisie</li></country><region><li>Gouvernorat de Tunis</li></region><settlement><li>Tunis</li></settlement></list><tree><noCountry><name sortKey="Abidi, Naima" sort="Abidi, Naima" uniqKey="Abidi N" first="Naima" last="Abidi">Naima Abidi</name><name sortKey="Ben Abderrazek, Rahma" sort="Ben Abderrazek, Rahma" uniqKey="Ben Abderrazek R" first="Rahma" last="Ben Abderrazek">Rahma Ben Abderrazek</name><name sortKey="Benlasfar, Zakaria" sort="Benlasfar, Zakaria" uniqKey="Benlasfar Z" first="Zakaria" last="Benlasfar">Zakaria Benlasfar</name><name sortKey="Bouhaouala Zahar, Balkiss" sort="Bouhaouala Zahar, Balkiss" uniqKey="Bouhaouala Zahar B" first="Balkiss" last="Bouhaouala-Zahar">Balkiss Bouhaouala-Zahar</name><name sortKey="El Ayeb, Mohamed" sort="El Ayeb, Mohamed" uniqKey="El Ayeb M" first="Mohamed" last="El Ayeb">Mohamed El Ayeb</name><name sortKey="Govaert, Jochen" sort="Govaert, Jochen" uniqKey="Govaert J" first="Jochen" last="Govaert">Jochen Govaert</name><name sortKey="Muyldermans, Serge" sort="Muyldermans, Serge" uniqKey="Muyldermans S" first="Serge" last="Muyldermans">Serge Muyldermans</name><name sortKey="Saerens, Dirk" sort="Saerens, Dirk" uniqKey="Saerens D" first="Dirk" last="Saerens">Dirk Saerens</name><name sortKey="Vincke, Cecile" sort="Vincke, Cecile" uniqKey="Vincke C" first="Cécile" last="Vincke">Cécile Vincke</name></noCountry><country name="Tunisie"><region name="Gouvernorat de Tunis"><name sortKey="Hmila, Issam" sort="Hmila, Issam" uniqKey="Hmila I" first="Issam" last="Hmila">Issam Hmila</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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