Compositions that Include Hemagglutinin, Methods of Making and Methods of Use Thereof

Abstract

Compositions comprise a flagellin component that is at least a portion of a flagellin, wherein the flagellin component includes at least one cysteine residue and whereby the flagellin component activates a Toll-like Receptor 5. Compositions can further include an antigen, such as an influenza antigen. The compositions are used to stimulate an immune response and a protective immune response in a subject.

1 . A composition comprising at least a portion of a  S. typhimurium  flagellin, wherein the  S. typhimurium  flagellin includes at least one cysteine residue and activates a Toll-like Receptor 5. 
     
     
         2 . The composition of  claim 1 , wherein the cysteine residue is remote to at least one amino acid of the Toll-like Receptor 5 recognition site of the  S. typhimurium  flagellin. 
     
     
         3 . The composition of  claim 1 , further including at least a portion of at least one influenza antigen. 
     
     
         4 . The composition of  claim 1 , wherein the influenza antigen includes at least a portion of a hemagglutinin influenza antigen. 
     
     
         5 . The composition of  claim 4 , wherein the portion of the hemagglutinin protein includes at least a portion of a maturational cleavage site of the hemagglutinin protein. 
     
     
         6 . The composition of  claim 1 , wherein the  S. typhimurium  flagellin includes at least a portion of SEQ ID NO: 810. 
     
     
         7 . The composition of  claim 1 , wherein at least one cysteine residue substitutes for at least one amino acid in a naturally occurring flagellin amino acid sequence of the  S. typhimurium  flagellin. 
     
     
         8 . A composition comprising a Toll-like Receptor agonist component that is at least a portion of a Toll-like Receptor agonist, wherein the Toll-like Receptor agonist component includes at least one cysteine residue in a position where a cysteine residue does not occur in the native Toll-like Receptor agonist, whereby the Toll-like Receptor agonist component activates a Toll-like Receptor. 
     
     
         9 . A composition comprising a flagellin component that is at least a portion of a flagellin, wherein at least one lysine of the flagellin component has been substituted with at least one arginine, whereby the flagellin component activates a Toll-like Receptor 5.