Compositions and methods for treating viral infections

Abstract

The present disclosure provides compositions and methods useful for treating viral infections. As described herein, the compositions and methods are based on the development of immunogenic compositions that include an inactivated virus in combination with a non-ionic surfactant vesicle (NISV). In certain embodiments at least a portion of the antigen present in the composition is physically associated with the NISV. In certain embodiments the compositions are lyophilized and subsequently rehydrated after a period of storage. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV. In certain embodiments the lyophilized compositions are stored at temperatures in excess of 8° C. prior to rehydration. In certain embodiments the rehydrated compositions exhibit greater potency as compared to otherwise equivalent compositions that lack the NISV and that were also stored at temperatures in excess of 8° C. prior to rehydration. In certain embodiments the antigen is taken from a licensed vaccine and the administered dose of antigen is less than the standard human dose for the licensed vaccine.

What is claimed is: 
     
         1 . A thermostable lyophilized immunogenic composition comprising:
 an inactivated viral antigen; and   a vesicle which comprises a non-ionic surfactant.   
     
     
         2 . The composition of  claim 1 , where the composition comprises an inactivated polio virus, an inactivated rabies virus, an inactivated hepatitis A virus, or a combination thereof. 
     
     
         3 . The composition of  claim 1  or  2 , wherein the non-ionic surfactant is an ester-linked surfactant. 
     
     
         4 . The composition of  claim 3 , wherein the non-ionic surfactant is a glycerol ester. 
     
     
         5 . The composition of  claim 3 , wherein the non-ionic surfactant is 1-monopalmitoyl glycerol. 
     
     
         6 . The composition of  claim 1  or  2 , wherein the non-ionic surfactant is an ether-linked surfactant. 
     
     
         7 . The composition of  claim 6 , wherein the non-ionic surfactant is a glycol or glycerol monoether. 
     
     
         8 . The composition of  claim 6 , wherein the non-ionic surfactant is 1-monocetyl glycerol ether or diglycolcetyl ether. 
     
     
         9 . The composition of  claim 1  or  2 , where the vesicle further comprises an ionic amphiphile. 
     
     
         10 . The composition of  claim 9 , where the ionic amphiphile is an alkanoic acid or an alkenoic acid. 
     
     
         11 . The composition of  claim 9 , where the ionic amphiphile is a phosphate. 
     
     
         12 . The composition of  claim 9 , where the ionic amphiphile is dicetylphospate, phosphatidic acid or phosphatidyl serine. 
     
     
         13 . The composition of  claim 9 , where the ionic amphiphile is a sulphate monoester. 
     
     
         14 . The composition of  claim 9 , where the ionic amphiphile is cetylsulphate. 
     
     
         15 . The composition of  claim 1  or  2 , where the vesicle further comprises a steroid. 
     
     
         16 . The composition of  claim 15 , where the steroid is cholesterol. 
     
     
         17 . The composition of  claim 1  or  2 , wherein the vesicle comprises 1-monopalmitoyl glycerol, dicetylphospate and cholesterol. 
     
     
         18 . The composition of any one of the preceding claims, wherein at least a portion of the virus is associated with the vesicle. 
     
     
         19 . The composition of any one of the preceding claims, wherein the virus is encapsulated within an aqueous core of the vesicle. 
     
     
         20 . A method of treating an individual suffering from, or at risk for, infection from a viral infection, the method comprising:
 providing a composition of any one of  claim 1 - 19  or  28 - 39 , wherein the composition has been stored for a period of time at a temperature in excess of 8° C.;   rehydrating the composition with an aqueous solution; and   administering to the individual a therapeutically effective amount of the rehydrated composition.   
     
     
         21 . The method of  claim 20 , wherein the individual is suffering from, or at risk for, infection from a polio virus, a rabies virus, a hepatitis A virus, or combination thereof. 
     
     
         22 . The method of  claim 20 , wherein the composition has been stored for a period of time at a temperature in excess of 25° C. 
     
     
         23 . The method of  claim 20 , wherein the composition has been stored for a period of time at a temperature in excess of 30° C. 
     
     
         24 . The method of  claim 20 , wherein the composition has been stored for a period of time at a temperature in excess of 35° C. 
     
     
         25 . The method of any one of  claims 20 - 24 , wherein the composition is administered by intramuscular injection. 
     
     
         26 . The method of any one of  claims 20 - 24 , wherein the composition is administered by subcutaneous injection. 
     
     
         27 . The method of  claim 20 , wherein the composition elicits an immune response in the individual at a first level that is higher than a second level of an immune response elicited by a second composition comprising the antigen and lacking the vesicle. 
     
     
         28 . The composition of any one of  claims 1 - 19 , wherein the composition is prepared by a method that includes:
 melting lipids that include the non-ionic surfactant to produce molten lipids;   combining the molten lipids with an aqueous solution that includes the virus antigen; and   homogenizing the resulting product, wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration of at least about 5 mg/ml in the resulting product.   
     
     
         29 . The composition of  claim 28 , wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration in a range of about 5 mg/ml to about 100 mg/ml in the resulting product. 
     
     
         30 . A composition comprising an inactivated viral antigen and vesicles, wherein the vesicles are comprised of lipids that include a non-ionic surfactant and the composition is prepared by a method that includes:
 melting the lipids to produce molten lipids;   combining the molten lipids with an aqueous solution that includes the inactivated viral antigen; and   homogenizing the resulting product, wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration of at least about 5 mg/ml in the resulting product.   
     
     
         31 . The composition of  claim 30 , wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration in a range of about 5 mg/ml to about 100 mg/ml in the resulting product. 
     
     
         32 . The composition of  claim 30  or  31 , wherein the molten lipids are added to the aqueous solution that includes the inactivated viral antigen. 
     
     
         33 . The composition of  claim 30  or  31 , wherein the aqueous solution that includes the inactivated viral antigen is added to the molten lipids. 
     
     
         34 . The composition of any one of  claim 1 - 19  or  28 - 33 , wherein the composition was prepared by a method that involved storing the composition in dried form. 
     
     
         35 . The composition of  claim 34 , wherein the composition in dried form was not stored under temperature-controlled conditions. 
     
     
         36 . The composition of  claim 34 , wherein the composition in dried form was stored at a temperature that at least temporarily exceeded 8° C. 
     
     
         37 . The composition of  claim 34 , wherein the composition in dried form was stored at a temperature that at least temporarily exceeded 15° C. 
     
     
         38 . The composition of  claim 34 , wherein the composition in dried form was stored at a temperature that at least temporarily exceeded 20° C. 
     
     
         39 . The composition of  claim 34 , wherein the composition in dried form was stored at a temperature that at least temporarily exceeded 25° C. 
     
     
         40 . A method of preparing a composition comprising an inactivated viral antigen and vesicles, wherein the lipid vesicles are comprised of lipids that include a non-ionic surfactant, the method comprising:
 melting the lipids to produce molten lipids;   combining the molten lipids with an aqueous solution that includes the inactivated viral antigen; and   homogenizing the resulting product, wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration of at least about 5 mg/ml in the resulting product.   
     
     
         41 . The method of  claim 40 , wherein the molten lipids and aqueous solution are combined in relative amounts and volumes that achieve a lipid concentration in a range of about 5 mg/ml to about 100 mg/ml in the resulting product. 
     
     
         42 . The method of  claim 40  or  41 , wherein the molten lipids are added to the aqueous solution that includes the inactivated viral antigen. 
     
     
         43 . The method of  claim 36  or  37 , wherein the aqueous solution that includes the inactivated viral antigen is added to the molten lipids.