Adjuvant compositions

Abstract

Adjuvant compositions comprising type 1 interferon inducers, such as double-stranded RNA, in combination with antigen delivery systems and/or immunostimulatory molecules, such as immunostimulatory nucleic acid sequences, for enhancing the immune response of a coadministered antigen, are described.

1 . A composition comprising (a) a dsRNA, (b) a submicron oil-in-water emulsion and (c) a protein antigen, wherein the composition is capable of increasing the immune response to the antigen as compared to delivery of the antigen and dsRNA alone without the submicron oil-in-water emulsion. 
     
     
         2 . The composition of  claim 1 , wherein the dsRNA is selected from polyriboinosinic-polyribocytidylic acid (poly[rI-rC]), polyriboguanylic-polyribocytidylic acid (poly[rG-rC]) or polyriboadenylic-polyribouridylic acid (poly[rA-rU]). 
     
     
         3 . The composition of  claim 2 , wherein the dsRNA is poly[rI-rC]. 
     
     
         4 . The composition of  claim 1 , wherein the antigen is associated with a microparticle. 
     
     
         5 . The composition of  claim 4 , wherein the antigen is adsorbed to a microparticle comprising poly(D,L-lactide-co-glycolide) (PLG). 
     
     
         6 . The composition of  claim 1 , wherein the dsRNA is associated with a microparticle. 
     
     
         7 . The composition of  claim 6 , wherein the dsRNA is adsorbed to a microparticle comprising poly(D,L-lactide-co-glycolide) (PLG). 
     
     
         8 . The composition of  claim 1 , wherein the submicron oil-in-water emulsion comprises (a) a metabolizable oil, wherein oil is present in an amount of 1% to 12% of the total volume and (b) an emulsifying agent, wherein the emulsifying agent is present in an amount of 0.01% to 1% by weight (w/v), and wherein the oil and the emulsifying agent are present in the form of an oil-in-water emulsion having oil droplets substantially all of which are about 100 nm to less than 1 micron in diameter. 
     
     
         9 . The composition of  claim 8 , wherein the emulsifying agent comprises polyoxyethylene sorbitan mono-, di-, or triester and/or a sorbitan mono-, di-, or triester. 
     
     
         10 . The composition of  claim 8 , wherein the submicron oil-in-water emulsion comprises 4-5% w/v squalene, 0.25-1.0% w/v polyoxyethylenesorbitan monooleate, and/or 0.25-1.0% sorbitan trioleate. 
     
     
         11 . The composition of  claim 8 , wherein the submicron oil-in-water emulsion consists essentially of 5% by volume of squalene; and one or more emulsifying agents selected from the group consisting of polyoxyethylenesorbitan monooleate and sorbitan trioleate, wherein the total amount of emulsifying agent(s) present is 1% by weight (w/v). 
     
     
         12 . The composition of  claim 11 , wherein the one or more emulsifying agents are polyoxyethylenesorbitan monooleate and sorbitan trioleate and the total amount of polyoxyethylenesorbitan monooleate and sorbitan trioleate present is 1% by weight (w/v). 
     
     
         13 . A method of stimulating an immune response in a vertebrate subject, said method comprising administering to the subject a therapeutically effective amount of a composition according to  claim 1 . 
     
     
         14 . A method of stimulating an immune response in a vertebrate subject, said method comprising administering to the subject a therapeutically effective amount of a composition according to  claim 10 . 
     
     
         15 . A method of making a composition comprising combining a dsRNA, a submicron oil-in-water emulsion, and a protein antigen.