A bispecific nanobody to provide full protection against lethal scorpion envenoming.
Identifieur interne : 000715 ( PubMed/Corpus ); précédent : 000714; suivant : 000716A bispecific nanobody to provide full protection against lethal scorpion envenoming.
Auteurs : Issam Hmila ; 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.
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
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pubmed:20410443Le document en format XML
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Pasteur, BP-74, 1002 Tunis, Tunisia.</nlm:affiliation></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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:20410443</idno><idno type="pmid">20410443</idno><idno type="doi">10.1096/fj.09-148213</idno><idno type="wicri:Area/PubMed/Corpus">000715</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000715</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A bispecific nanobody to provide full protection against lethal scorpion envenoming.</title><author><name sortKey="Hmila, Issam" sort="Hmila, Issam" uniqKey="Hmila I" first="Issam" last="Hmila">Issam Hmila</name><affiliation><nlm:affiliation>Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Pl. Pasteur, BP-74, 1002 Tunis, Tunisia.</nlm:affiliation></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="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" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Epitope Mapping</term><term>Male</term><term>Mice</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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20410443</PMID><DateCompleted><Year>2010</Year><Month>09</Month><Day>21</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1530-6860</ISSN><JournalIssue CitedMedium="Internet"><Volume>24</Volume><Issue>9</Issue><PubDate><Year>2010</Year><Month>Sep</Month></PubDate></JournalIssue><Title>FASEB journal : official publication of the Federation of American Societies for Experimental Biology</Title><ISOAbbreviation>FASEB J</ISOAbbreviation></Journal><ArticleTitle>A bispecific nanobody to provide full protection against lethal scorpion envenoming.</ArticleTitle><Pagination><MedlinePgn>3479-89</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1096/fj.09-148213</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hmila</LastName><ForeName>Issam</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Pl. Pasteur, BP-74, 1002 Tunis, Tunisia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saerens</LastName><ForeName>Dirk</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Ben Abderrazek</LastName><ForeName>Rahma</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Vincke</LastName><ForeName>Cécile</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Abidi</LastName><ForeName>Naima</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Benlasfar</LastName><ForeName>Zakaria</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Govaert</LastName><ForeName>Jochen</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>El Ayeb</LastName><ForeName>Mohamed</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Bouhaouala-Zahar</LastName><ForeName>Balkiss</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Muyldermans</LastName><ForeName>Serge</ForeName><Initials>S</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>04</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>FASEB J</MedlineTA><NlmUniqueID>8804484</NlmUniqueID><ISSNLinking>0892-6638</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007128">Immunoglobulin Fragments</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012604">Scorpion Venoms</NameOfSubstance></Chemical><Chemical><RegistryNumber>12584-90-6</RegistryNumber><NameOfSubstance UI="C065314">scorpion toxin I, Androctonus</NameOfSubstance></Chemical><Chemical><RegistryNumber>37309-04-9</RegistryNumber><NameOfSubstance UI="C053969">scorpion toxin II, Androctonus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002162" MajorTopicYN="N">Camelus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018604" MajorTopicYN="N">Epitope Mapping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007128" MajorTopicYN="N">Immunoglobulin Fragments</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012604" MajorTopicYN="N">Scorpion Venoms</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>4</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>4</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>9</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20410443</ArticleId><ArticleId IdType="pii">fj.09-148213</ArticleId><ArticleId IdType="doi">10.1096/fj.09-148213</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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