Papillomavirus vaccine compositions

Abstract

The present invention relates to pharmaceutical compositions comprising virus-like particles (VLPs) of HPV, said VLPs adsorbed to an aluminum adjuvant, and an ISCOM-type adjuvant comprising a saponin, cholesterol, and a phospholipid. In preferred embodiments, the aluminum adjuvant comprises amorphous aluminum hydroxyphosphate sulfate. Another aspect of the invention provides multi-dose HPV vaccine formulations comprising HPV VLPs and an antimicrobial preservative selected from the group consisting of: m-cresol, phenol and benzyl alcohol. Also provided are methods of using the disclosed pharmaceutical compositions and formulations to induce an immune response against HPV in a human patient and to prevent HPV infection.

1 - 27 . (canceled) 
     
     
         28 . A human papillomavirus (HPV) vaccine composition comprising HPV virus-like particles (VLPs) of HPV types 6, 11, 16, 18, 31, 45, 52, and 58 and an aluminum adjuvant, wherein the HPV VLPs are adsorbed onto said aluminum adjuvant. 
     
     
         29 . The HPV vaccine composition of  claim 28 , further comprising VLPs of at least one additional HPV type. 
     
     
         30 . The HPV vaccine composition of  claim 29 , wherein the at least one additional HPV type is selected from the group consisting of HPV26, HPV33, HPV35, HPV39, HPV51, HPV53, HPV55, HPV56, HPV59, HPV66, HPV68, HPV73, and HPV82. 
     
     
         31 . A human papillomavirus (HPV) vaccine composition consisting of HPV virus-like particles (VLPs) of HPV types 6, 11, 16, 18, 31, 45, 52, 58 and one additional HPV type and an aluminum adjuvant, wherein each of said HPV VLPs is present in a concentration of about 40 μg/ml to about 80 μg/ml, wherein the HPV VLPs are adsorbed onto said aluminum adjuvant and wherein the one additional HPV type is selected from the group consisting of: HPV26, HPV33, HPV35, HPV39, HPV51, HPV53, HPV55, HPV56, HPV59, HPV66, HPV68, HPV73, and HPV82. 
     
     
         32 . The HPV vaccine composition of  claim 28 , wherein the HPV VLPs consist of HPV types 6, 11, 16, 18, 31, 45, 52, and 58 and VLPs of one additional HPV type selected from the group consisting of: HPV26, HPV33, HPV35, HPV39, HPV51, HPV53, HPV55, HPV56, HPV59, HPV66, HPV68, HPV73, and HPV82. 
     
     
         33 . The HPV vaccine composition of  claim 32 , wherein the HPV VLPs consist of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. 
     
     
         34 . The HPV vaccine composition of  claim 28 , further comprising a second adjuvant, wherein the second adjuvant comprises a saponin, cholesterol, and a phospholipid. 
     
     
         35 . The HPV vaccine composition of  claim 31 , wherein the vaccine comprises a second adjuvant, wherein the second adjuvant comprises a saponin, cholesterol, and a phospholipid.