INVENTOR(S)- LANGERMANN, Solomon, R. 6606 Cross Country Boulevard, Baltimore, MD 20878 United States of America
INVENTOR(S)- HULTGREN, Scott, J. 1068 Polo Downs, Town and Country, MO 63017 United States of America
INVENTOR(S)- HUNG, Chia-Suei 1425 Cutter Avenue, St. Louis, MO 63139 United States of America
INVENTOR(S)- BOUCKAERT, Julie 7549 Trenton Avenue, St. Louis, MO 63130 United States of America

APPLICANT(S)- MEDIMMUNE, INC. 35 West Watkins Mill Road, Gaithersburg, MD 20878 United States of America
DATE FILED- 2001-12-10
PUBLICATION NUMBER- 02102974 WO
PUBLICATION DATE- 2002-12-27
ATTORNEY, AGENT, OR FIRM- POISSANT, Brian, M., Pennie & Edmonds LLP, 1155 Avenue of the Americas, New York, NY 10036, United States of America INTERNATIONAL PATENT CLASS- C12N
PCT APP. NO.- PCT/US01/47994

The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response, It particularly relates to the vaccination of mammalian species, especially human patients, with variants of theE coli FimCH protein that elicit antibodies that have better functional inhibitory activity than antibodies raised against wild type protein . In particular, such variants include mutations that promote a more open confirmation of the FimH protein , particularly in regions involved in mannose binding, to expose regions previously poorly exposed and mutations that abolish a significantly reduce mannose binding. In another aspect, the invention provides antibodies against such proteins and protein complexes that may be used in passive immunization to protect or treat pathogenic bacterial infections. The present invention also provides machine readable media embedded with the three-dimensional atomic structure coordinates of FimCH bound to mannose, and subsets thereof, and methods of using the crystal structure to provide candidate amino acid residues for mutation.