Serveur d'exploration SRAS

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Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.

Identifieur interne : 001B39 ( PubMed/Curation ); précédent : 001B38; suivant : 001B40

Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.

Auteurs : J. Rogers [États-Unis] ; R J Schoepp ; O. Schröder ; T L Clements ; T F Holland ; J Q Li ; J. Li ; L M Lewis ; R P Dirmeier ; G J Frey ; X. Tan ; K. Wong ; G. Woodnutt ; M. Keller ; D S Reed ; B E Kimmel ; E C Tozer

Source :

RBID : pubmed:18480090

Descripteurs français

English descriptors

Abstract

Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5-4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.

DOI: 10.1093/protein/gzn027
PubMed: 18480090

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Links to Exploration step

pubmed:18480090

Le document en format XML

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<div type="abstract" xml:lang="en">Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5-4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.</div>
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