Flagellin Fusion Proteins and Use Thereof to Induce Immune Responses Against Pseudomonas aeruginosa

Abstract

The invention provides compositions and fusion proteins comprising a flagellin adjuvant and a Pseudomonas aeruginosa antigen. The invention further provides pharmaceutical formulations and methods for inducing an immune response against P. aeruginosa (e.g., to prevent and/or treat P. aeruginosa infection).

That which is claimed is: 
     
         1 . A fusion protein comprising:
 (a) a  Pseudomonas aeruginosa  type A flagellin adjuvant and/or a  Pseudomonas aeruginosa  type B flagellin adjuvant; and   (b) a  Pseudomonas aeruginosa  antigen.   
     
     
         2 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type A flagellin adjuvant and/or a  Pseudomonas aeruginosa  type B flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprF antigen and/or a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         3 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type A flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         4 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type B flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         5 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type A flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprF antigen. 
 
     
     
         6 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type B flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprF antigen. 
 
     
     
         7 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type A flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprF antigen and a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         8 . The fusion protein of  claim 1  comprising:
 (a) a  Pseudomonas aeruginosa  type B flagellin adjuvant; and 
 (b) a  Pseudomonas aeruginosa  OprF antigen and a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         9 . The fusion protein of clans  7 , wherein the fusion protein comprises a fusion peptide comprising the OprF antigen and the OprI antigen. 
     
     
         10 . A composition comprising:
 (a) a fusion protein comprising (i) a  Pseudomonas aeruginosa  type A flagellin adjuvant; and (ii) a  Pseudomonas aeruginosa  antigen; and   (b) a fusion protein comprising (i) a  Pseudomonas aeruginosa  type B flagellin adjuvant; and (ii) a  Pseudomonas aeruginosa  antigen.   
     
     
         11 . The composition of  claim 10  comprising:
 (a) a fusion protein comprising (i) a  Pseudomonas aeruginosa  type A flagellin adjuvant; and (ii) a  Pseudomonas aeruginosa  OprF antigen and/or a  Pseudomonas aeruginosa  OprI antigen; and 
 (b) a fusion protein comprising (i) a  Pseudomonas aeruginosa  type B flagellin adjuvant; and (ii) a  Pseudomonas aeruginosa  OprF antigen and/or a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         12 . The composition of  claim 10  comprising:
 (a) a fusion protein comprising (i) a  Pseudomonas aeruginosa  type A flagellin adjuvant; and (ii) a  Pseudomonas aeruginosa  OprF antigen and a  Pseudomonas aeruginosa  OprI antigen; and 
 (b) a fusion protein comprising (i) a  Pseudomonas aeruginosa  type B flagellin adjuvant; and (ii) a  Pseudomonas aeruginosa  OprF antigen and a  Pseudomonas aeruginosa  OprI antigen. 
 
     
     
         13 . The fusion protein of  claim 1 , wherein the  Pseudomonas aeruginosa  antigen(s) is an N-terminal extension of the flagellin adjuvant. 
     
     
         14 . The fusion protein of  claim 1 , wherein the  Pseudomonas aeruginosa  antigen(s) is between the N-terminal constant region and the C-terminal constant region of the flagellin adjuvant. 
     
     
         15 . The fusion protein of  claim 14 , wherein the flagellin adjuvant(s) comprises a deleted hypervariable region or the hypervariable region is absent from the flagellin adjuvant(s). 
     
     
         16 . The fusion protein of  claim 14 , wherein the  Pseudomonas aeruginosa  antigen(s) is inserted (i) within the hypervariable region, (ii) between the N-terminal constant region and the hypervariable region, or (iii) between the C-terminal constant region and the hypervariable region. 
     
     
         17 . A nucleic acid encoding the fusion protein of  claim 1 . 
     
     
         18 . A vector comprising the nucleic acid of  claim 17 . 
     
     
         19 . A host cell comprising the nucleic acid of  claim 17 . 
     
     
         20 . A method of making the fusion protein of  claim 1 , the method comprising culturing a host cell in a culture medium under conditions sufficient for the fusion protein to be produced.