Immunostimulatory compositions
The present disclosure relates to immunostimulatory compositions that are effective in eliciting immune responses in avian species. More specifically, these immunostimulatory compositions comprise an immunomodulator composition and an immunostimulatory oligonucleotide that when administered.
1. An immunostimulatory oligonucleotide comprising at least one CpG motif and a guanine nucleotide enriched sequence beginning at or within four nucleotides of the 5′ terminus of the immunostimulatory oligonucleotide, wherein the guanine nucleotide enriched sequence comprises TTAGGG, TTAGGGTTAGGG (SEQ ID NO:261), TTTTGGGG, GGGGTTTT, GGGGTTTTGGGG (SEQ ID NO:262), TTAGGG, TTAGGGTTAGGGTTTT (SEQ ID NO: 263), TGTGGGTGTGTGTGGG (SEQ ID NO:269), GGAGG, TGGAGGC, TGGAGGCTGGAGGC (SEQ ID NO:264), or TGGGGT.
2. An immunostimulatory composition comprising the immunostimulatory oligonucleotide of claim 1 and a pharmaceutical carrier.
3. A method of preparing the immunostimulatory composition of claim 2 comprising:
combining the immunostimulatory oligonucleotide with a pharmaceutical carrier to form an immunostimulatory composition;
centrifuging the immunostimulatory composition to generate a supernatant and a pellet; and
isolating the pellet.
4. A method for stimulating toll-like receptor 21 (TLR21) comprising
administering the immunostimulatory oligonucleotide of claim 1 .
5. The method of claim 4 , wherein the immunostimulatory oligonucleotide comprises a ligand for TLR21.
6. A method of eliciting an immune response in a subject comprising administering to the subject the immunostimulatory oligonucleotide of claim 1 .
7. A vector comprising the oligonucleotide of claim 1 .
8. The method of claim 4 , wherein the oligonucleotide further comprises a G-wire sequence.
9. The method of claim 8 , wherein the G-wire sequence comprises SEQ ID NO: 141, 142, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 252, or GCGT-Gwire3.
10. A method of eliciting an immune response in a subject comprising administering to a subject in need thereof the immunostimulatory composition of claim 2 .
11. An immunostimulatory oligonucleotide comprising at least one CpG motif and a guanine nucleotide enriched sequence beginning at or within four nucleotides of the 5′ terminus of the immunostimulatory oligonucleotide,
wherein the immunostimulatory oligonucleotide comprises SEQ ID NO: 16, 17, 18, 19, 20, 21, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 77, 78, 81, 82, 85, 86, 89, 90, 92, 93, 96, 97, 100, 102, 104, 106, 108, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 124, 125, 126, 127, 129, 130, 131, 134, 136, 137, 138, 141, 142, 143, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203 or 252.
12. A vector comprising the oligonucleotide of claim 11 .
13. A method for stimulating toll-like receptor 21 (TLR21) comprising: administering the immunostimulatory oligonucleotide of claim 11 .
14. The method of claim 13 , wherein the immunostimulatory oligonucleotide comprises a ligand for TLR21.
15. A method of eliciting an immune response in a subject comprising administering to the subject the immunostimulatory oligonucleotide of claim 11 .
16. The method of claim 15 , wherein the oligonucleotide further comprises a G-wire sequence.
17. The method of claim 16 , wherein the G-wire sequence comprises SEQ ID NO: 141, 142, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 252, or GCGT-Gwire3.
18. An immunostimulatory composition comprising the immunostimulatory oligonucleotide of claim 11 and a pharmaceutical carrier.
19. A method of eliciting an immune response in a subject comprising administering to a subject in need thereof the immunostimulatory composition of claim 18 .
20. A method of preparing the immunostimulatory composition of claim 18 comprising:
combining the immunostimulatory oligonucleotide with a pharmaceutical carrier to form an immunostimulatory composition;
centrifuging the immunostimulatory composition to generate a supernatant and a pellet; and
isolating the pellet.