Immunogen platform
Aspects of the present invention relate to chimeric polypeptides including HCV NS3/4A sequences and T-cell epitopes. Embodiments include nucleic acids encoding the chimeric NS3/4A polypeptides, the encoded polypeptides, compositions containing said nucleic acids, compositions containing said chimeric polypeptides, as well as methods of making and using the aforementioned compositions including, but not limited to medicaments and vaccines.
1. A nucleic acid comprising a nucleotide sequence encoding a chimeric protein comprising a hepatitis C virus (HCV) NS3/4A antigen fused to a birch allergen.
2. The nucleic acid of claim 1 , wherein said birch allergen is a Betv1 birch allergen.
3. The nucleic acid of claim 1 , wherein said birch allergen comprises a sequence selected from the group consisting of SEQ ID NO: 1062, SEQ ID NO: 1125, and SEQ ID NO: 1146.
4. The nucleic acid of claim 1 , wherein said chimeric protein further comprises at least one HCV NS3 protease cleavage site.
5. The nucleic acid of claim 4 , wherein at least one HCV NS3 protease cleavage site is inserted between said NS3/4A antigen and said birch allergen.
6. The nucleic acid of claim 4 , wherein at least one HCV NS3 protease cleavage exists is inserted within said birch allergen.
7. The nucleic acid of claim 4 , wherein said NS3 protease cleavage site comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1177, SEQ ID NO: 1179, SEQ ID NO: 1340, SEQ ID NO: 1341, SEQ ID NO: 1342, SEQ ID NO: 1343, SEQ ID NO: 1344, SEQ ID NO: 1345, SEQ ID NO: 1346, SEQ ID NO: 1347, SEQ ID NO: 1348, SEQ ID NO: 1349, SEQ ID NO: 1350, SEQ ID NO: 1351, SEQ ID NO: 1352, SEQ ID NO: 1353, SEQ ID NO: 1354, SEQ ID NO: 1355, SEQ ID NO: 1356, SEQ ID NO: 1357, SEQ ID NO: 1358, SEQ ID NO: 1359, SEQ ID NO: 1360, SEQ ID NO: 1361, SEQ ID NO: 1362, SEQ ID NO: 1363, SEQ ID NO: 1364, SEQ ID NO: 1365, SEQ ID NO: 1366, SEQ ID NO: 1367, SEQ ID NO: 1368, SEQ ID NO: 1369, SEQ ID NO: 1370, SEQ ID NO: 1371, SEQ ID NO: 1372, SEQ ID NO: 1373, SEQ ID NO: 1374, SEQ ID NO: 1375, SEQ ID NO: 1376, SEQ ID NO: 1377, and SEQ ID NO: 1378.
8. The nucleic acid of claim 1 , wherein said nucleotide sequence comprises the sequence set forth in SEQ ID NO: 1380.
9. The nucleic acid of claim 1 , wherein said nucleotide sequence comprises the sequence set forth in SEQ ID NO: 1381.
10. The nucleic acid of claim 2 , wherein said nucleic acid primes interferon gamma producing Betv 1-specific T cells in vivo.
11. The nucleic acid of claim 2 , wherein said nucleic acid does not prime IgE antibodies.
12. A nucleic acid comprising a nucleotide sequence encoding a chimeric protein comprising a hepatitis C virus (HCV) NS3/4A antigen fused to a Betv 1 birch allergen, wherein said chimeric protein comprises at least one HCV NS3 protease cleavage site.
13. The nucleic acid of claim 12 , wherein at least one HCV NS3 protease cleavage site is inserted between said NS3/4A antigen and said birch allergen.
14. The nucleic acid of claim 12 , wherein at least one HCV NS3 protease cleavage site is inserted within said birch allergen.
15. The nucleic acid of claim 12 , wherein said nucleic acid primes interferon gamma producing Betv 1-specific T cells in vivo but does not prime Betv 1-specific IgE antibodies.
16. A plasmid comprising a polynucleotide comprising a nucleotide sequence encoding a chimeric protein comprising a hepatitis C virus (HCV) NS3/4A antigen fused to a birch allergen.