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About:
Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice
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wasabi.inria.fr
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Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
title
Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice
Creator
Logunov, Denis
Naroditsky, Boris
Shcheblyakov, Dmitry
Solovyev, Andrey
Tukhvatulin, Amir
Esmagambetov, Ilias
Gintsburg, Aleksandr
Godakova, Svetlana
Noskov, Anatoly
Ugriumova, Galina
Vinogradova, Irina
source
Medline; PMC
abstract
The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD(50)) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD(50). Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A.
has issue date
2019-08-07
(
xsd:dateTime
)
bibo:doi
10.3390/toxins11080464
bibo:pmid
31394847
has license
cc-by
sha1sum (hex)
7f3637433b7c8dff7fc35f0b5e67794877bce0c1
schema:url
https://doi.org/10.3390/toxins11080464
resource representing a document's title
Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice
has PubMed Central identifier
PMC6723419
has PubMed identifier
31394847
schema:publication
Toxins (Basel)
resource representing a document's body
covid:7f3637433b7c8dff7fc35f0b5e67794877bce0c1#body_text
is
schema:about
of
named entity 'times'
named entity 'sequences'
named entity 'produced'
named entity 'selected'
covid:arg/7f3637433b7c8dff7fc35f0b5e67794877bce0c1
named entity 'BOTULINUM NEUROTOXIN'
named entity 'DEMONSTRATED'
named entity 'CHALLENGES'
named entity 'TYPE A'
named entity 'MODIFICATION'
named entity 'CLONE'
named entity 'CLOSTRIDIUM BOTULINUM'
named entity 'NOVEL'
named entity 'INTOXICATION'
named entity 'TIME'
named entity 'FCS'
named entity 'SEVERE'
named entity 'HIGHER'
named entity 'LONG TERM'
named entity 'CAUSATIVE AGENT'
named entity 'RESULTS'
named entity 'PHAGE DISPLAY'
named entity 'DIFFERENT'
named entity 'SINGLE-DOMAIN ANTIBODIES'
named entity 'NERVOUS SYSTEM'
named entity 'TIMES'
named entity 'BASED'
named entity 'BLOOD'
named entity 'DISPLAY TECHNOLOGY'
named entity 'USED'
named entity 'SEQUENCES'
named entity 'HUMAN IMMUNOGLOBULIN G'
named entity 'ACTIVITY'
named entity 'DAMAGE'
named entity '1000'
named entity 'POTENCY'
named entity 'THEIR'
named entity 'CIRCULATION'
named entity 'IN VIVO'
named entity 'CAUSED BY'
named entity 'HUMAN'
named entity 'FUSED TO'
named entity 'PROTECTION'
named entity 'CHARACTERISTICS'
named entity 'STUDY'
named entity 'IMMUNOTHERAPEUTICS'
named entity 'BACTERIUM'
named entity 'FRAGMENTS'
named entity 'REGION 3'
named entity 'LONG TERM'
named entity 'CAMELID'
named entity 'UNIQUE'
named entity 'CAMELID'
named entity 'EFFORT'
named entity 'CHECK'
named entity 'CHARACTERIZED'
named entity 'DAYS'
named entity 'ANTITOXIN'
named entity 'ADMINISTRATION'
named entity 'BOTULISM'
named entity 'THESE'
named entity 'COULD BE'
named entity 'PHAGE'
named entity 'FRAGMENT'
named entity 'BOTULINUM NEUROTOXIN'
named entity 'SELECTED'
named entity 'ANTIBODY'
named entity 'PROTECTION'
named entity 'MONOCLONAL'
named entity 'EFFECTIVE'
named entity 'LETHAL DOSE'
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