Skip Navigation



PEDS Advance Access published online on June 8, 2004
Protein Engineering Design and Selection, doi:10.1093/protein/gzh043
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/4/391    most recent
gzh043v1
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 PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Olson, M. A.
Right arrow Articles by Millard, C. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olson, M. A.
Right arrow Articles by Millard, C. B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received May 3, 2004
Accepted May 10, 2004

Article

Finding a new vaccine in the ricin protein fold

Mark A. Olson 1, John H. Carra 1, Virginia Roxas-Duncan 1, Robert W. Wannemacher 1, Leonard A. Smith 1, Charles B. Millard 1*

1 United States Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, MD 21702-5011

* To whom correspondence should be addressed. E-mail: charles.b.millard{at}us.army.mil.


  Abstract

Previous attempts to produce a vaccine for ricin toxin have been hampered by safety concerns arising from residual toxicity, and the undesirable aggregation or precipitation caused by exposure of hydrophobic surfaces on the ricin A-chain (RTA) in the absence of its natural B-chain partner. We undertook a structure-based solution to this problem by reversing evolutionary selection on the "ribosome inactivating protein" fold of RTA to arrive at a non-functional, compacted single-domain scaffold (sequence RTA1-198) for presentation of a specific protective epitope (RTA loop 95-110). An optimized protein based upon our modeling design (RTA1-33/44-198) showed greater resistance to thermal denaturation, less precipitation under physiological conditions, and a reduction in toxic activity of at least three orders of magnitude compared with RTA. Most importantly, RTA1-198 or RTA1-33/44-198 protected 100% of vaccinated animals against supra-lethal challenge with aerosolized ricin. We conclude that comparative protein analysis and engineering yielded a superior vaccine by exploiting a component of the toxin that is inherently more stable than is the parent RTA molecule.

Keywords: Protein engineering, ribosome inactivating proteins, protein aggregation


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


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
E. S. Vitetta, J. E. Smallshaw, E. Coleman, H. Jafri, C. Foster, R. Munford, and J. Schindler
A pilot clinical trial of a recombinant ricin vaccine in normal humans
PNAS, February 14, 2006; 103(7): 2268 - 2273.
[Abstract] [Full Text] [PDF]


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.