Dsrnas as influenza virus vaccine adjuvants or immuno-stimulants

Abstract

Vaccine protection against acute or chronic viral infection is facilitated by using as an adjuvant or immuno-stimulant, a dsRNA together with an anti-influenza vaccine.

1 . A method of enhancing the immune response against an acute viral influenza infection of a first subtype, the method comprising:
 (i) co-administration of an inactive influenza vaccine of a second subtype, distinct from the first subtype and a mismatched dsRNA, or   (ii) administration of a composition comprising an inactive influenza vaccine of a second subtype, distinct from the first subtype and a mismatched dsRNA,   wherein the mismatched dsRNA is rI n ·r(C 12 ,U) n , in which n is an integer, rI is polyriboinosinic acid and r(C 12 ,U) is a polyribocytidylic acid sequence containing unpaired uracils,   wherein the mismatched dsRNA acts as an adjuvant or immuno-stimulant, and   wherein the method results in an enhanced immune response against the acute viral influenza infection of a first subtype compared to the administration of the inactive influenza vaccine of a second subtype without the mismatched dsRNA.   
     
     
         2 . The method of  claim 1 , wherein an enhanced immune response is determined by nasal wash viral titer. 
     
     
         3 . The method of  claim 1 , wherein the acute viral influenza infection of a first subtype is H5N1 avian influenza. 
     
     
         4 . The method of  claim 1 , wherein the acute viral influenza infection of a first subtype is H5N1 avian influenza and the inactive influenza vaccine of a second subtype, distinct from the first subtype, is a trivalent seasonal vaccine. 
     
     
         5 . The method of  claim 1 , wherein n is between 12 and 50. 
     
     
         6 . A method of enhancing the immune response against an acute viral influenza infection of a first subtype, the method comprising:
 (i) co-administration of an inactive influenza vaccine of a second subtype, distinct from the first subtype and a mismatched dsRNA, or (ii) administration of a composition comprising an inactive influenza vaccine of a second subtype, distinct from the first subtype and a mismatched dsRNA,   wherein the mismatched dsRNA is rI n ·r(C 12 ,U) n , in which n is an integer, rI is polyriboinosinic acid and r(C 12 ,U) is a polyribocytidylic acid sequence containing unpaired uracils,   wherein the mismatched dsRNA acts as an adjuvant or immuno-stimulant,   wherein the method results in an enhanced immune response against the acute viral influenza infection of a first subtype compared to the administration of the inactive influenza vaccine of a second subtype without the mismatched dsRNA,   wherein an enhanced immune response is determined by nasal wash viral titer, and   wherein the acute viral influenza infection of a first subtype is H5N1 avian influenza.   
     
     
         7 . The method of  claim 6 , wherein n is between 12 and 50. 
     
     
         8 . The method of  claim 7 , wherein the sedimentation coefficient is about 6.7. 
     
     
         9 . The method of  claim 1 , in which the dsRNA is additionally complexed with an RNA-stabilizing polymer. 
     
     
         10 . The method of,  claim 9 , in which the RNA-stabilizing polymer is lysine or cellulose. 
     
     
         11 . The method of  claim 2 , in which the dsRNA is additionally complexed with an RNA-stabilizing polymer. 
     
     
         12 . The method of  claim 12 , in which the RNA-stabilizing polymer is lysine or cellulose.