Prostate neoantigens and their uses
The disclosure relates to prostate neoantigens, polynucleotides encoding them, vectors, host cells, recombinant virus particles, vaccines comprising the neoantigens, proteinaceous molecules binding the prostate neoantigens, and methods of making and using them.
1. A vaccine comprising a heterologous polynucleotide encoding a heterologous polypeptide, wherein the heterologous polypeptide comprises the amino acid sequence of SEQ ID NOs: 541, 543, 550, 554, 555, 556, 623, 624, 552, 557, 558, 559, 625, or 626.
2. The vaccine of claim 1 , wherein the vaccine is capable of eliciting a cellular immune response in a subject administered the vaccine.
3. The vaccine of claim 2 , wherein the cellular immune response is activation of vaccine-specific CD8 + T cells, CD4 + T cells, or CD8 + T cells and CD4 + T cells, wherein activation is assessed by increased production of TNFα, IFNγ, or TNFα and IFNγ by the CD8 + T cells, the CD4 + T cells, or the CD8 + T cells and CD4 + T cells.
4. The vaccine of claim 1 , wherein the heterologous polynucleotide comprises a promoter, an enhancer, a polyadenylation site, a Kozak sequence, a stop codon, a T cell enhancer (TCE), or any combination thereof.
5. The vaccine of claim 4 , wherein the promoter comprises a CMV promoter or a vaccinia P7.5 promoter.
6. The vaccine of claim 5 , wherein the TCE is encoded by a polynucleotide of SEQ ID NO: 546, the CMV promoter comprises a polynucleotide of SEQ ID NO: 628, the vaccinia P7.5 promoter comprises a polynucleotide of SEQ ID NO: 630 and the polyadenylation site comprises a bovine growth hormone polyadenylation site of SEQ ID NO: 629.
7. The vaccine of claim 1 , wherein the heterologous polynucleotide comprises the polynucleotide sequence of SEQ ID NO: 542, SEQ ID NO: 544, SEQ ID NO: 551, or SEQ ID NO: 553.
8. The vaccine of claim 1 , wherein the heterologous polynucleotide is DNA or RNA.
9. The vaccine of claim 8 , wherein RNA is mRNA or self-replicating RNA.
10. The vaccine of claim 7 , wherein the heterologous polynucleotide is DNA or RNA.
11. The vaccine of claim 10 , wherein RNA is mRNA or self-replicating RNA.
12. The vaccine of claim 1 , wherein the vaccine is a recombinant virus.
13. The vaccine of claim 12 , wherein the recombinant virus is derived from adenovirus (Ad), poxvirus, adeno-associated virus (AAV) or retrovirus.
14. The vaccine of claim 13 , wherein the recombinant virus is derived from hAd5, hAd7, hAd11, hAd26, hAd34, hAd35, hAd48, hAd49, hAd50, GAd20, GAd19, GAd21, GAd25, GAd26, GAd27, GAd28, GAd29, GAd30, GAd31, ChAd3, ChAd4, ChAd5, ChAd6, ChAd7, ChAd8, ChAd9, ChAd10, ChAd11, ChAd16, ChAd17, ChAd19, ChAd20, ChAd22, ChAd24, ChAd26, ChAd30, ChAd31, ChAd37, ChAd38, ChAd44, ChAd55, ChAd63, ChAd73, ChAd82, ChAd83, ChAd146, ChAd147, PanAdl, PanAd2, PanAd3, Copenhagen vaccinia virus (W), New York Attenuated Vaccinia Virus (NYVAC), ALVAC, TROVAC, or modified vaccinia ankara (MVA).
15. The vaccine of claim 14 , wherein the recombinant virus is derived from GAd20.
16. The vaccine of claim 14 , wherein the recombinant virus is derived from MVA.
17. The vaccine of claim 14 , wherein the recombinant virus is derived from hAd26.
18. A vaccine comprising a heterologous polynucleotide encoding a heterologous polypeptide, wherein the heterologous polypeptide comprises the amino acid sequence of SEQ ID NOs: 541, 550, 554, 555, 556, 623, or 624.
19. The vaccine of claim 18 , wherein the heterologous polynucleotide comprises the polynucleotide sequence of SEQ ID NOs: 542 or 551.
20. The vaccine of claim 18 , wherein the vaccine is a recombinant virus derived from GAd20.
21. A vaccine comprising a heterologous polynucleotide encoding a heterologous polypeptide, wherein the heterologous polypeptide comprises the amino acid sequence of SEQ ID NOs: 543, 552, 557, 558, 559, 625, or 626.
22. The vaccine of claim 21 , wherein the heterologous polynucleotide comprises the polynucleotide sequence of SEQ ID NO: 544 or 553.
23. The vaccine of claim 21 , wherein the vaccine is a recombinant virus derived from MVA.
24. The vaccine of claim 18 , wherein the heterologous polypeptide comprises the amino acid sequence of SEQ ID NO: 541.
25. The vaccine of claim 24 , wherein the vaccine is self-replicating RNA or a recombinant virus derived from GAd20, MVA, or hAd26.
26. The vaccine of claim 25 , wherein the vaccine is a recombinant virus derived from GAd20.
27. The vaccine of claim 21 , wherein the heterologous polypeptide comprises the amino acid sequence of SEQ ID NO: 543.
28. The vaccine of claim 27 , wherein the vaccine is self-replicating RNA or a recombinant virus derived from GAd20, MVA, or hAd26.
29. The vaccine of claim 28 , wherein the vaccine is a recombinant virus derived from MVA.