Fusion proteins and methods of use

Abstract

Compositions that include at least three fusion proteins comprising flagellin and influenza antigens. In embodiments, the influenza antigens can include influenza A and influenza B antigens. The composition can further include at least one adjuvant.

What is claimed is: 
     
         1 . A composition comprising at least three fusion proteins that each activate a Toll-like Receptor 5, wherein:
 (a) a first fusion protein includes a first flagellin and a first influenza A viral hemagglutinin antigen that has an isoelectric point greater than about 6.0 fused to a portion of the first flagellin;   (b) a second fusion protein includes a second flagellin and a second influenza A viral hemagglutinin antigen that is distinct from the first influenza A viral hemagglutinin antigen and that has an isoelectric point greater than about 7.0 fused to a portion of the second flagellin; and   (c) a third fusion protein includes a third flagellin and a first influenza B viral hemagglutinin antigen that has an isolectric point greater than about 8.0 and is fused to at least one loop of domain 3 of the third flagellin.   
     
     
         2 . The composition of  claim 1 , further including at least one adjuvant. 
     
     
         3 . The composition of  claim 1 , wherein:
 (a) the first influenza A viral hemagglutinin antigen includes at least a portion or the entirety of an HA1 subunit that has at least a portion of a globular head that includes at least one β-sheet at a bottom of the globular head;   (b) the second influenza A viral hemagglutinin antigen includes at least a portion or the entirety of an HA1 subunit having at least a portion of a globular head that includes at least one β-sheet, at least one β-sandwich and at least two β-strands at the bottom of the portion of the globular head; and   (c) the first influenza B viral hemagglutinin antigen includes at least a portion or the entirety of an HA1 subunit that has at least a portion of a globular head that includes at least one β-sheet at a bottom of the globular head.   
     
     
         4 . The composition of  claim 1 , further including a fourth fusion protein that activates a Toll-like Receptor 5, the fourth fusion protein comprising a second influenza B viral hemagglutinin antigen that is distinct from the first influenza B viral hemagglutinin antigen and that has an isoelectric point greater than about 8.0 fused to at least one loop of domain 3 in the fourth flagellin. 
     
     
         5 . The composition of  claim 4 , wherein the second influenza B viral hemagglutinin antigen includes at least a portion or the entirety of an HA1 subunit that has at least a portion of a globular head that includes at least one β-sheet at a bottom of the globular head.