Novel hpv16 non hla-restricted t-cell vaccines, compositions and methods of use thereof

Abstract

Novel human papillomovirus immunogenic compositions and methods of use thereof are provided. The compositions comprise unique combinations of multi-epitope peptide sequences specifically selected and designed to be effectively processed and cross-presented to T-cells. The peptides utilized in the compositions display high levels of binding with HLA-supertypes. The immunogenic compositions are broadly applicable to large proportions of target populations. The compositions comprise adjuvants such as cationic lipids.

What is claimed is: 
     
         1 . A vaccine composition comprising peptide antigens and an adjuvant,
 wherein the peptide antigens comprise at least 2 different HPV peptides selected from the group consisting of: a peptide comprising SEQ ID NO: 5, a peptide comprising SEQ ID NO: 9, a peptide comprising SEQ ID NO: 10, and a peptide comprising SEQ ID NO: 11, a peptide comprising SEQ ID NO: 23, a peptide comprising SEQ ID NO: 24, a peptide comprising SEQ ID NO: 25, a peptide comprising SEQ ID NO: 26, or combinations thereof,   wherein each peptide has a binding affinity of approximately IC50 of 5,000 nM with 5 HLA supertypes, wherein at least one peptide antigen is a multi-epitope peptide antigen, and wherein the adjuvant comprises a cationic lipid.   
     
     
         2 . The vaccine composition of  claim 1 , wherein the peptide antigens are individual peptide antigens. 
     
     
         3 . The vaccine composition of  claim 1 , wherein the peptide antigens are conjugated to each other. 
     
     
         4 . The vaccine composition of  claim 3 , further comprising a spacer. 
     
     
         5 . The vaccine composition of  claim 1 , further comprising at least one single epitope peptide antigen selected from the group consisting of: a peptide comprising SEQ ID NO: 14, a peptide comprising SEQ ID NO: 15, a peptide comprising SEQ ID NO: 27, a peptide comprising SEQ ID NO: 28, or a combination thereof. 
     
     
         6 . The vaccine composition of  claim 1 , wherein the cationic lipid is selected from the group consisting of: DOTAP, DDA, DOEPC, DOTMA, R-DOTAP, R-DDA, R-DOEPC, R-DOTMA, S-DOTAP, S-DDA, S-DOEPC, S-DOTMA, variations or analogs thereof. 
     
     
         7 . The vaccine composition of  claim 6 , wherein the cationic lipid comprises R-DOTAP. 
     
     
         8 . The vaccine composition of  claim 1 , wherein the peptide antigens are encapsulated in liposomes comprising the cationic lipid. 
     
     
         9 . The vaccine composition of  claim 1 , wherein the HLA supertypes selected from the group consisting of HLA-A*02:01, HLA-A*03:01, HLA-A*24:02, HLA-B*07:02, and HLA-B*58:01. 
     
     
         10 . A method of inducing an immune response against an HPV infection in a subject comprising administering to the subject a vaccine composition comprising peptide antigens and an adjuvant,
 wherein the peptide antigens comprise at least 2 different HPV peptides selected from the group consisting of: a peptide comprising SEQ ID NO: 5, a peptide comprising SEQ ID NO: 9, a peptide comprising SEQ ID NO: 10, and a peptide comprising SEQ ID NO: 11, a peptide comprising SEQ ID NO: 23, a peptide comprising SEQ ID NO: 24, a peptide comprising SEQ ID NO: 25, a peptide comprising SEQ ID NO: 26, or combinations thereof,   wherein each peptide has a binding affinity of approximately IC50 of 5,000 nM with 5 HLA supertypes, wherein at least one peptide antigen is a multi-epitope peptide antigen, and wherein the adjuvant comprises a cationic lipid, thereby inducing an immune response to an HPV infection.   
     
     
         11 . The method of  claim 10 , wherein the adjuvant comprises a cationic lipid selected from the group consisting of: DOTAP, DDA, DOEPC, DOTMA, R-DOTAP, R-DDA, R-DOEPC, R-DOTMA, S-DOTAP, S-DDA, S-DOEPC, S-DOTMA, variations or analogs thereof. 
     
     
         12 . The method of  claim 11 , wherein the cationic lipid comprises R-DOTAP. 
     
     
         13 . The method of  claim 10 , wherein the immune response is an induction of CD8+ T -cells. 
     
     
         14 . The method of  claim 10 , wherein the immune response is at least 2-fold over baseline. 
     
     
         15 . A method of treating an HPV infection in a subject comprising administering to the subject a vaccine composition comprising peptide antigens and an adjuvant,
 wherein the peptide antigens comprise at least 2 different HPV peptides selected from the group consisting of: a peptide comprising SEQ ID NO: 5, a peptide comprising SEQ ID NO: 9, a peptide comprising SEQ ID NO: 10, and a peptide comprising SEQ ID NO: 11, a peptide comprising SEQ ID NO: 23, a peptide comprising SEQ ID NO: 24, a peptide comprising SEQ ID NO: 25, a peptide comprising SEQ ID NO: 26, or combinations thereof,   wherein each peptide has a binding affinity of approximately IC50 of 5,000 nM with 5 HLA supertypes, wherein at least one peptide antigen is a multi-epitope peptide antigen, and wherein the adjuvant comprises a cationic lipid, thereby treating the HPV infection.   
     
     
         16 . The method of  claim 15 , wherein the adjuvant comprises a cationic lipid selected from the group consisting of: DOTAP, DDA, DOEPC, DOTMA, R-DOTAP, R-DDA, R-DOEPC, R-DOTMA, S-DOTAP, S-DDA, S-DOEPC, S-DOTMA, variations or analogs thereof. 
     
     
         17 . The method of  claim 16 , wherein the cationic lipid comprises R-DOTAP. 
     
     
         18 . The method of  claim 15 , wherein the HPV infection comprises symptoms selected from the group consisting of: common warts, plantar warts, flat warts, genital warts, anogenital warts, anal dysplasia, vulva cancer, vaginal cancer, cervical cancer, penile cancer, anal cancer, cancers of the head and neck, epidermaodysplasia verruciformis, focal epithelias hyperplasia, mouth papillomas, oropharyngeal cancer, verrucous cyst, laryngeal papillomatosis and combinations thereof. 
     
     
         19 . The method of  claim 15 , wherein administration of the vaccine composition results in tumor regression.