HUMAN PAPILLOMAVIRUS VACCINES AND USES OF THE SAME
Multi-antigenic human papilloma virus (HPV) molecular vaccine constructs for use and treatment of HPV-associated disorders and pathologies, such as HPV molecular vaccines targeting HPV16-, HPV18-, and HPV-45-associated pathologies.
1 . (canceled)
2 . The method of claim 34 , wherein the fusion protein comprises:
(a) an HPV-16 E5 peptide comprising the amino acid sequence of SEQ ID NO: 130;
(b) an HPV-16 E6 peptide comprising the amino acid sequence of any one of SEQ ID NOs: 113-121;
(c) an HPV-18 E6 peptide comprising the amino acid sequence of any one of SEQ ID NOs: 131-138;
(d) an HPV-16 E7 peptide comprising the amino acid sequence of any one of SEQ ID NOs: 122-129; and/or
(e) an HPV-18 E7 peptide comprising the amino acid sequence of any one of SEQ ID NOs: 139-144.
3 - 7 . (canceled)
8 . The method of claim 34 , wherein the fusion protein further comprises an agonist peptide comprising the amino acid sequence of any one of SEQ ID NOs: 145-147.
9 . The method of claim 34 , wherein the fusion protein further comprises an ankyrin-like repeat domain.
10 - 11 . (canceled)
12 . The method of claim 34 , wherein the fusion protein comprises an amino acid sequence having at least 90% identity with any one of SEQ ID NOs: 51-53 and 243.
13 . The method of claim 34 , wherein the fusion protein comprises an amino acid sequence having at least 95% identity with any one of SEQ ID NOs: 51-53 and 243.
14 - 16 . (canceled)
17 . The method of claim 34 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 243 or a conservatively-substituted variant thereof.
18 . The method of claim 34 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 243.
19 - 23 . (canceled)
24 . The method of claim 34 , comprising administering a vector comprising the polynucleotide.
25 - 26 . (canceled)
27 . The method of claim 24 , wherein the vector is an adenoviral vector is deficient in one or more elements selected from an E1-E4 region and an L1-L5 region.
28 . (canceled)
29 . The method of claim 24 , wherein the vector is a gorilla adenoviral vector.
30 . The method of claim 24 , wherein the vector is a GC46 gorilla adenoviral vector.
31 . (canceled)
32 . A method of inducing an anti-HPV immune response in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding a fusion protein, the fusion protein comprising:
(a) an HPV-16 E5 peptide or an HPV-18 E5 peptide; and
(b) an HPV-16 E6 peptide, an HPV-16 E7 peptide, an HPV-18 E6 peptide, or an HPV-18 E7 peptide.
33 . (canceled)
34 . A method of treating an HPV-associated disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a polynucleotide encoding a fusion protein, the fusion protein comprising:
(a) an HPV-16 E5 peptide or an HPV-18 E5 peptide; and
(b) an HPV-16 E6 peptide, an HPV-16 E7 peptide, an HPV-18 E6 peptide, or an HPV-18 E7 peptide.
35 . The method of claim 34 , wherein the HPV-associated disease or disorder is an HPV-16 associated disease or disorder, an HPV-18 associated disease or disorder, or an HPV-45 associated disease or disorder.
36 . The method of claim 34 , wherein the HPV-associated disease or disorder is an HPV-associated cancer.
37 . The method of claim 36 , wherein the HPV-associated cancer is a lower genital tract neoplasia, a cervical cancer, a vulvar cancer, an anal cancer, a penile cancer, or a head and neck cancer.
38 . The method of claim 29 , wherein the therapeutically effective amount comprises about 0.1×10 9 to about 10×10 12 particle units.
39 . (canceled)
40 . The method of claim 34 , further comprising administering: an anti-inflammatory agent; an analgesic; a biological response modifier; a cytokine; an interferon; an interleukin; a CAR-T cell; a bifunctional protein; a colony-stimulating factor; a tumor necrosis factor; a surface active agent; a small molecule enzyme inhibitor; a chemotherapy agent; and/or an anti-metastatic agent.
41 . The method of claim 34 , further comprising administering a biological response modifier and/or a chemotherapy agent.
42 . The method of claim 34 , further comprising administering an immune checkpoint inhibitor.
43 - 50 . (canceled)