Vaccine composition containing synthetic adjuvant

Abstract

Compositions and methods, including vaccines and pharmaceutical compositions for inducing or enhancing an immune response are disclosed based on the discovery of useful immunological adjuvant properties in a synthetic, glucopyranosyl lipid adjuvant (GLA) that is provided in substantially homogeneous form. Chemically defined, synthetic GLA offers a consistent vaccine component from lot to lot without the fluctuations in contaminants or activity that compromise natural-product adjuvants. Also provided are vaccines and pharmaceutical compositions that include GLA and one or more of an antigen, a Toll-like receptor (TLR) agonist, a co-adjuvant and a carrier such as a pharmaceutical carrier.

1 - 34 . (canceled) 
     
     
         35 . A pharmaceutical composition for inducing or enhancing an immune response against herpes simplex virus comprising:
 (a) at least one herpes simplex virus antigen; and   (b) a lipid adjuvant of the formula:   
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 3 , R 5  and R 6  are C 11 -C 20  alkyl; and 
 R 2  and R 4  are C 12 -C 20  alkyl; or a pharmaceutically acceptable salt thereof. 
 
     
     
         36 . The composition of  claim 35 , wherein the at least one herpes simplex virus antigen comprises at least one HSV-1 or HSV-2 antigen. 
     
     
         37 . The composition of  claim 35 , wherein the at least one herpes simplex virus antigen comprises whole live or inactivated virus. 
     
     
         38 . The composition of  claim 35 , wherein the at least one herpes simplex virus antigen comprises at least one purified or recombinant herpes simplex virus antigen selected from the group consisting of an HSV immediate early protein, an HSV ICP27 protein and an HSV gD protein, or combinations thereof. 
     
     
         39 . The composition of  claim 35 , wherein the alkyl is straight chain saturated alkyl. 
     
     
         40 . The composition of  claim 35 , wherein R 1 , R 3 , R 5  and R 6  are undecyl and R 2  and R 4  are tridecyl. 
     
     
         41 . The composition of  claim 35 , wherein the lipid adjuvant is synthetic. 
     
     
         42 . The composition of  claim 35 , wherein the lipid adjuvant is at least 80% pure based on the total weight of lipid adjuvant species in the composition. 
     
     
         43 . The composition of  claim 35 , wherein the lipid adjuvant is at least 95% pure based on the total weight of lipid adjuvant species in the composition. 
     
     
         44 . The composition of  claim 35 , further comprising a pharmaceutically acceptable carrier or excipient. 
     
     
         45 . The composition of  claim 35 , which is in a form of an oil-in-water emulsion, a water-in-oil emulsion, a liposome, or a microparticle. 
     
     
         46 . The composition of  claim 35 , which is in a form of an oil-in-water emulsion and the oil is a metabolizable oil. 
     
     
         47 . The composition of  claim 46 , wherein the oil is squalene. 
     
     
         48 . The composition of  claim 35 , further comprising an antioxidant. 
     
     
         49 . The composition of  claim 35 , further comprising alpha-tocopherol. 
     
     
         50 . The composition of  claim 35 , further comprising oil and alpha-tocopherol where the oil:alpha-tocopherol are present in a ratio of equal to or less than 1. 
     
     
         51 . The composition of  claim 35 , which has been sterile filtered. 
     
     
         52 . The composition of  claim 35 , which is in the form of a stable aqueous suspension of less than 0.2 um and further comprises at least one component selected from the group consisting of phospholipids, fatty acids, surfactants, detergents, saponins, and fluorodated lipids. 
     
     
         53 . A method for inducing or enhancing an immune response against a herpes simplex virus comprising the steps of administering to a subject in need thereof a composition of any one of  claims 35 - 52 .