Adjuvant composition and methods for its use

Abstract

An adjuvant composition which is a stable oil-in-water emulsion comprising a metabolizable oil, one or more surfactants, an antioxidant and a compound to make the emulsion isotonic is described and claimed. The stable emulsion has a hydrophobic-lipophilic balance (HLB) of from about 7.5 to about 10.5 and a particle size of less than 3 μm. In a preferred embodiment, the stable emulsion comprises 10% volume to volume squalene, 0.09% weight to volume PLURONIC F-68 block co-polymer, 1.9% weight to volume egg phosphatidyl choline, 1.75% volume to volume glycerol and 0.05% weight to volume α tocopherol. The preferred emulsion has a HLB of 8.0 and a particle size of about 0.2 μm. In a particularly preferred embodiment, the stable emulsion is combined with an attenuated lipid A derivative such as monophosphoryl lipid A or 3-deacylated monophosphoryl lipid A to enhance the adjuvanticity of the composition.

1 . An adjuvant composition comprising a metabolizable oil, one or more surfactants, an antioxidant and a component to make said composition isotonic.  
     
     
         2 . The adjuvant composition of  claim 1 , wherein said metabolizable oil is selected from a group consisting of squalene, soybean oil, sesame oil and MIGLYOL 810 oil.  
     
     
         3 . The adjuvant composition of  claim 1 , wherein said metabolizable oil is squalene.  
     
     
         4 . The adjuvant composition of  claim 1 , wherein said one or more surfactants is selected from the group consisting of Tween 80, CAMPUL POE-O low PV surfactant, SOLITOL HS15 surfactant, PLURONIC F68 block co-polymer, sodium cholate, glycerodeoxy cholate, sphingomyelin, sphingosine, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, L-α-phosphatidylethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and egg phosphatidyl choline, or a mixture thereof.  
     
     
         5 . The adjuvant composition of  claim 1 , wherein said one or more surfactants are a mixture of egg phosphatidyl choline and PLURONIC F-68 block co-polymer.  
     
     
         6 . The adjuvant composition of  claim 1 , wherein said antioxidant is selected from the group consisting of a tocopherol and ascorbic acid.  
     
     
         7 . The adjuvant composition of  claim 1 , wherein said antioxidant is α tocopherol.  
     
     
         8 . The adjuvant composition of  claim 1 , wherein said component to make said emulsion isotonic is selected from the group consisting of dextrose, glycerol, mannitol, sorbitol, PEG 300, PEG 400 and polyethylene glycol.  
     
     
         9 . The adjuvant composition of  claim 1 , wherein said component to make said emulsion isotonic is glycerol.  
     
     
         10 . The adjuvant composition of  claim 1 , wherein said composition is an oil-in-water emulsion.  
     
     
         11 . The adjuvant composition of  claim 1 , wherein said emulsion has a hydrophobic-lipophilic balance of from about 7.5 to about 13.0.  
     
     
         12 . The adjuvant composition of  claim 1 , wherein said emulsion has a hydrophobic-lipophilic balance of about 8.0.  
     
     
         13 . The adjuvant composition of  claim 1 , wherein said stable emulsion comprises about 10% volume to volume squalene, 0.09% weight to volume PLURONIC F-68 block co-polymer, 1.9% weight to volume egg phosphatidyl choline, 1.75% volume to volume glycerol and 0.05% weight to volume a tocopherol.  
     
     
         14 . The adjuvant composition of  claim 1 , further comprising an attenuated lipid A derivative.  
     
     
         15 . The adjuvant composition of  claim 14 , wherein said attenuated lipid A derivative is selected from the group consisting of monophosphoryl lipid A and 3-deacylated monophosphoryl lipid A.  
     
     
         16 . The adjuvant composition of  claim 14 , wherein said attenuated lipid A derivative is monophosphoryl lipid A.  
     
     
         17 . The adjuvant composition of  claim 14 , wherein said attenuated lipid A derivative is 3-deacylated monophosphoryl lipid A.  
     
     
         18 . The adjuvant composition of  claim 14 , wherein said attenuated lipid A derivative is about 1.200% to about 0.005% weight to volume of said stable emulsion.  
     
     
         19 . A vaccine composition comprising an antigen and an adjuvant composition comprising a metabolizable oil, one or more surfactants, an antioxidant and a component to make said emulsion isotonic.  
     
     
         20 . The vaccine composition of 19, wherein said stable emulsion comprises about 10% volume to volume squalene, 0.09% weight to volume PLURONIC F68 block co-polymer, 1.9% weight to volume egg phosphatidyl choline, 1.75% volume to volume glycerol and 0.05% weight to volume a tocopherol.  
     
     
         21 . The vaccine composition of 19, wherein said stable emulsion further comprises an attenuated lipid A derivative selected from the group consisting of monophosphoryl lipid A and 3-deacylated monophosphoryl lipid A.  
     
     
         22 . A method for stimulating the immune response of a warm-blooded animal comprising administering to the animal an antigen and an effective amount of a stable oil-in-water emulsion comprising a metabolizable oil, one or more surfactants, an antioxidant and a component to make said emulsion isotonic.  
     
     
         23 . The method of  claim 22 , wherein said stable emulsion comprises about 10% volume to volume squalene, 0.09% weight to volume PLURONIC F68 block co-polymer, 1.9% weight to volume egg phosphatidyl choline, 1.75% volume to volume glycerol and 0.05% weight to volume a tocopherol.  
     
     
         24 . The method of  claim 22 , wherein said emulsion further comprises an attenuated lipid A derivative selected from the group consisting of monophosphoryl lipid A and 3-deacylated monophosphoryl lipid A.