Skip Navigation


PEDS Advance Access originally published online on May 13, 2008
Protein Engineering Design and Selection 2008 21(8):495-505; doi:10.1093/protein/gzn027
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
21/8/495    most recent
gzn027v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Rogers, J.
Right arrow Articles by Tozer, E.C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rogers, J.
Right arrow Articles by Tozer, E.C.
Related Collections
Right arrow 2008
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases

J. Rogers1,{dagger}, R.J. Schoepp2, O. Schröder1,{dagger}, T.L. Clements2, T.F. Holland1,{dagger}, J.Q. Li1,{dagger}, J. Li1,{dagger}, L.M. Lewis1,{dagger}, R.P. Dirmeier1, G.J. Frey1,{dagger}, X. Tan1, K. Wong1,{dagger}, G. Woodnutt1,{dagger}, M. Keller1,{dagger}, D.S. Reed3, B.E. Kimmel1,{dagger} and E.C. Tozer1,4

1 Verenium Corporation, 4955 Directors Place, San Diego, CA 92121 2Diagnostic Systems Division 3Department of Animal Studies, U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA

4 To whom correspondence should be addressed. E-mail: eileen.tozer{at}yahoo.com

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 HuFRTM (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.

Keywords: antibody discovery/humanized/optimized/SARS-CoV

Received December 7, 2007; revised April 16, 2008; accepted April 18, 2008.

{dagger} No longer at Verenium


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.