University of Washington

Institute for Systems Biology

University for Systems Biology

David M Underhill

Alan Arnold Aderem

Adrian Ozinsky

Fumitaka Hayashi

Kelly D Smith

The invention provides methods to elicit an immune response with an immunomodulatory flagellin polypeptide having toll-like receptor 5 (TLR5) binding, and further comprising an ADCC targeting molecule.

Toll-like receptor 5 ligands and methods of use

The invention provides an immunomodulatory flagellin peptide having substantially the same amino acid sequence GALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQ (SEQ ID NO:44), or a modification thereof, and having toll like receptor 5 (TLR5) binding. The immunomodulatory flagellin peptide also can have substantially the same amino acid sequence TQFSGVKVLAQDNTLTIQVGANDGETIDIDLKQINS QTLGLDTL (SEQ ID NO:45); EGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLNEIDRVNG (SEQ ID NO:46) or MAQVINTNSLSLLTQNNLNKSQSALGTAIERLSSGLRINSAKDDAAGQAIANF TANIKGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAVQS (SEQ ID NO:47), or a modification thereof. Also provided is an immunomodulatory flagellin peptide having substantially the same amino acid sequence LQKIDAALAQVDTLRSDLGAVQNRFNSAITNL (SEQ ID NO:48), or a modification thereof, and having toll like receptor 5 (TLR5) binding. The immunomodulatory flagellin peptide also can have substantially the same amino acid sequence TLRSDLGAVQNRFNSAITNLGNTVNNLSS (SEQ ID NO:49) or EQAAKTTENPLQKIDAALAQVDTLRSDLGAVQNRFNSAITNLGNTVNNLSS (SEQ ID NO:50), or a modification thereof. Further provided is an immunomodulatory flagellin peptide having substantially the same amino acid sequence GALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAE ITQ (SEQ ID NO:44) and substantially the same amino acid sequence LQKIDAALAQVDTLRSDLGAVQNRFNSAITNL (SEQ ID NO:48), or a modification thereof, and having toll like receptor 5 (TLR5) binding. Methods of using immunomodulatory flagellin peptides additionally are provided.

The invention provides an immunomodulatory flagellin peptide having at least about 10 amino acids of substantially the amino acid sequence GAVQNRFNSAIT (SEQ ID NO:2), or a modification thereof, and having toll-like receptor 5 (TLR5) binding. Methods of inducing an immune response are also provided.

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Seattle, WA, United States of America

David M Underhill