Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.
Identifieur interne : 001B39 ( PubMed/Corpus ); précédent : 001B38; suivant : 001B40Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.
Auteurs : J. Rogers ; 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 TozerSource :
- Protein engineering, design & selection : PEDS [ 1741-0126 ] ; 2008.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (genetics), Antibodies, Viral (isolation & purification), Antibodies, Viral (therapeutic use), Antibody Specificity (immunology), Chlorocebus aethiops, Communicable Diseases, Emerging (prevention & control), Communicable Diseases, Emerging (therapy), Directed Molecular Evolution (methods), Drug Discovery, Humans, Mice, Mice, Inbred BALB C, Neutralization Tests, Point Mutation (immunology), SARS Virus (immunology), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (therapy), Vero Cells.
- MESH :
- chemical , genetics : Antibodies, Viral.
- chemical , isolation & purification : Antibodies, Viral.
- chemical , therapeutic use : Antibodies, Viral.
- immunology : Antibody Specificity, Point Mutation, SARS Virus.
- methods : Directed Molecular Evolution.
- prevention & control : Communicable Diseases, Emerging, Severe Acute Respiratory Syndrome.
- therapy : Communicable Diseases, Emerging, Severe Acute Respiratory Syndrome.
- Animals, Chlorocebus aethiops, Drug Discovery, Humans, Mice, Mice, Inbred BALB C, Neutralization Tests, Vero Cells.
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
Links to Exploration step
pubmed:18480090Le document en format XML
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<front><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>
</front>
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<Abstract><AbstractText>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.</AbstractText>
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<Reference><Citation>Methods. 2005 May;36(1):43-60</Citation>
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