US Government As Represented by the Secretary of the Army

Mayo Foundation for Medical Education and Research

U.S. Army Medical Research and Material Command

Charles B Millard

Mark A Olson

Yuan-Ping Pang

James J Schmidt

Michael P Byrne

Jewn Giew Park

Robert W Wannemacher

Jaimee R Compton

Patricia M Legler

Rajesh K Mishra

Oksana Lockridge

Clarence A Broomfield

Shaohua Wang

Anuradha Vummenthala

Jon Davis

Jing Tang

Ross D LeClaire

Disclosed herein ricin toxin A chain polypeptides having an engineered disulfide bond ((SS)RTA) and compositions thereof. The disclosed (SS)RTA polypeptides retain the immunological epitope of wild type RTA, lack detectable N-glycosidase activity or exhibit reduced N-glycosidase activity as compared to controls, and exhibit increased solubility, thermal stability and a lower tendency to self-aggregate as compared to RTA 198 and/or RTA 1-33/44-198. Also disclosed are immunogenic compositions that may be used to immunize a subject against ricin intoxication. Methods of immunizing against, treating, inhibiting, reducing and/and preventing ricin intoxication are disclosed.

Ricin vaccine and methods of making thereof

Small-molecule inhibitors of Botulinum toxin, including BoNTA, BoNTD and BoNTE are provided, as well as methods of using the inhibitors.

Small-molecule botulinum toxin inhibitors

This disclosure relates to materials and methods for inhibiting Botulinum neurotoxin, and more particularly to materials and methods for inhibiting the zinc endopeptidase of Botulinum neurotoxin serotypes A, D and/or E (BoNTA, BoNTD and/or BoNTE).

Disclosed herein are polypeptides and variants thereof comprising a polypeptide sequence having substantial identity to ricin A chain (RTA) that lack detectable N-glycosidase-rRNA activity or exhibit reduced N-glycosidase-rRNA activity as compared to controls and methods of making and using thereof. The polypeptides and variants have a greater solubility in aqueous solutions of physiological pH and ionic strength than RTA and also retain the integrity of the neutralizing immunological epitope of wild type RTA. Also disclosed are immunogenic compositions that may be used to immunize a subject against ricin intoxication. Methods of immunizing against, treating, and preventing ricin intoxication are disclosed.

Ricin toxin A-chain fragment for use as a vaccine

Ricin vaccine and methods of making and using thereof

A method of modifying esterases by substitution with histadine of at least one amino acid within 6 .ANG. of an active site serine provides esterases useful for detoxifying organophasphates.

Site-directed mutagenesis of esterases

Growing community of inventors

Frederick, MD, United States of America

Charles B Millard