Flagellin Fusion Proteins

Abstract

Methods of making a protein that stimulates a protective immune response in a subject include separating a portion of a protein from a naturally occurring influenza viral hemagglutinin to form a protein portion.

1 . (canceled) 
     
     
         2 . A composition comprising at least a portion of at least one flagellin that initiates an intracellular signal transduction pathway for a Toll-like Receptor and a portion of a protein of a naturally occurring influenza viral hemagglutinin that lacks a transmembrane domain and a cytoplasmic domain, and includes at least a portion of a globular head and at least a portion of at least one secondary structure having at least one β-sheet at a bottom of the portion of the globular head that causes the portion of the globular head to essentially retain its tertiary structure. 
     
     
         3 . The composition of  claim 2 , further including a carrier protein. 
     
     
         4 . The composition of  claim 2 , wherein the flagellin and the portion of the naturally occurring influenza viral hemagglutinin are components of a fusion protein. 
     
     
         5 . The composition of  claim 2 , wherein the flagellin includes at least one member selected from the group consisting of  Salmonella typhimurium  flagellin, an  E coli  flagellin, a  S. muenchen  flagellin, a  Yersinia  flagellin, a  Campylobacter  flagellin, a  P. aeruginosa  flagellin and a  L. monocytogenes  flagellin. 
     
     
         6 . The composition of  claim 2 , wherein the flagellin includes a Toll-like Receptor 5 binding site, whereby the composition activates an innate response. 
     
     
         7 . The composition of  claim 2 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin includes an HA1-1 portion of the naturally occurring influenza viral hemagglutinin. 
     
     
         8 . The composition of  claim 2 , wherein the flagellin and the HA1-1 portion are components of a fusion protein. 
     
     
         9 . The composition of  claim 2 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin includes an HA1-2 portion of the naturally occurring influenza viral hemagglutinin. 
     
     
         10 . The composition of  claim 9 , wherein the flagellin and the HA1-2 protein portion are components of a fusion protein. 
     
     
         11 . The composition of  claim 2 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin is not glycosylated. 
     
     
         12 . The composition of  claim 2 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin further includes at least one β-sandwich at the bottom of the portion of the globular head. 
     
     
         13 . The composition of  claim 12 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin further includes at least two β-strands at the bottom of the portion of the globular head. 
     
     
         14 . The composition of  claim 2 , wherein the naturally occurring viral hemagglutinin is at least one member selected from the group consisting of a H1, H2, H3, H5, H7 and H9 strain. 
     
     
         15 . The composition of  claim 2 , wherein the naturally occurring influenza viral hemagglutinin is at least one member selected from the group consisting of an influenza A viral hemagglutinin and an influenza B viral hemagglutinin. 
     
     
         16 . The composition of  claim 2 , wherein the influenza viral hemagglutinin is the influenza C viral hemagglutinin. 
     
     
         17 . The composition of  claim 2 , wherein:
 i) the flagellin and the portion of the naturally occurring influenza viral hemagglutinin are components of a fusion protein that includes an amino acid linker between the flagellin and the portion of the naturally occurring influenza viral hemagglutinin; and   ii) the naturally occurring influenza viral hemagglutinin is a H3 strain.   
     
     
         18 . The composition of  claim 4 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin further includes at least one β-sandwich at the bottom of the portion of the globular head. 
     
     
         19 . The composition of  claim 18 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin further includes at least two β-strands at the bottom of the portion of the globular head. 
     
     
         20 . The composition of  claim 4 , wherein the fusion protein includes an amino acid linker between the flagellin and the portion of the naturally occurring influenza viral hemagglutinin. 
     
     
         21 . The composition of  claim 4 , wherein the naturally occurring viral hemagglutinin is at least one member selected from the group consisting of a H1, H2, H3, H5, H7 and H9 strain. 
     
     
         22 . The composition of  claim 21 , wherein the fusion protein includes an amino acid linker between the flagellin and the portion of the naturally occurring influenza viral hemagglutinin. 
     
     
         23 . The composition of  claim 4 , wherein the naturally occurring influenza viral hemagglutinin is at least one member selected from the group consisting of an influenza A viral hemagglutinin and an influenza B viral hemagglutinin. 
     
     
         24 . The composition of  claim 4 , wherein the influenza viral hemagglutinin is the influenza C viral hemagglutinin. 
     
     
         25 . The composition of  claim 4 , wherein the naturally occurring influenza viral hemagglutinin is a H3 strain. 
     
     
         26 . The composition of  claim 4 , wherein the portion of the protein of the naturally occurring influenza viral hemagglutinin is not glycosylated. 
     
     
         27 . The composition of  claim 4 , wherein the flagellin of the fusion protein includes a Toll-like Receptor 5 binding site, whereby the fusion protein activates an innate immune response.