Polyvalent, primary HIV-1 glycoprotein DNA vaccines and vaccination methods
View Patent ↗Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV is disclosed. The composition and methods described herein are for the use of a DNA composition that encodes one or more different HIV envelope glycoproteins. The DNA composition can encode an HIV Gag protein. The DNAs encoding one or more HIV proteins are a combination of different nucleic acids, such as DNA plasmids, generated from primary isolate DNA of different HIV major group genetic clades and/or different proteins. HIV protein compositions for inducing an immune response against HIV are disclosed. Methods fro using the protein compositions as boosts following administration of the DNA compositions are provided.
1. A method of inducing an immune response against human immunodeficiency virus (HIV) or an HIV epitope in a primate, the method comprising:
administering to the primate a nucleic acid composition comprising (a) at least four sets of nucleic acid molecules encoding wild-type HIV gp120 envelope glycoproteins, wherein the sets of nucleic acid molecules encode glycoproteins from primary isolates B715, Ba-L, and Czm, and from a clade E primary isolate, and (b) a set of nucleic acid molecules encoding a wild-type HIV gag protein from a primary isolate; and
thereafter administering to the primate a protein composition comprising a plurality of sets of isolated wild-type HIV envelope glycoprotein molecules of each of the primary isolates in (a),
wherein the nucleic acid composition and the protein composition are administered in amounts sufficient to induce an immune response against HIV or an HIV epitope in the primate.
2. The method of claim 1 , further comprising isolating immune cells from the primate; and testing an immune response of the isolated immune cells in vitro.
3. The method of claim 1 , wherein the protein composition is administered between 4 and 8 weeks after the nucleic acid composition.
4. The method of claim 1 , further comprising testing for a cell-mediated immune response.
5. The method of claim 1 , further comprising testing for a humoral immune response.
6. The method of claim 5 , wherein a neutralizing humoral response is tested.
7. The method of claim 1 , wherein a cell-mediated immune response is induced.
8. The method of claim 1 , wherein a humoral immune response is induced.
9. The method of claim 8 , wherein a neutralizing humoral immune response is induced.
10. The method of claim 1 , wherein the nucleic acid molecules comprise DNA plasmids.
11. The method of claim 1 , wherein one or more of the sets of nucleic acid molecules comprises optimized codons.
12. The method of claim 1 , wherein the set of nucleic acid molecules encoding the gag protein comprises optimized codons.
13. The method of claim 1 , wherein the protein composition is administered with an adjuvant.
14. The method of claim 13 , wherein the adjuvant is QS-21.
15. The method of claim 1 , wherein the clade E primary isolate is 93TH976.17.
16. The method of claim 1 , wherein the wild-type HIV gag protein is a gag protein of NL4-3.
17. A method of inducing an immune response against human immunodeficiency virus (HIV) or an HIV epitope in a human, the method comprising:
administering to the human a nucleic acid composition comprising (a) at least four sets of nucleic acid molecules encoding wild-type HIV gp120 envelope glycoproteins, wherein the sets of nucleic acid molecules encode glycoproteins from primary isolates B715, Ba-L, and Czm, and from a clade E primary isolate, and (b) a set of nucleic acid molecules encoding a wild-type HIV gag protein from a primary isolate; and
thereafter administering to the human a protein composition comprising a plurality of sets of isolated wild-type HIV envelope glycoprotein molecules of each of the primary isolates in (a),
wherein the nucleic acid composition and the protein composition are administered in amounts sufficient to induce an immune response against HIV or an HIV epitope in the human.
18. The method of claim 17 , wherein the nucleic acid composition further comprises a set of nucleic acid molecules encoding gp120 envelope glycoprotein of a primary isolate from clade A, and the protein composition further comprises a set of isolated envelope glycoprotein molecules of a primary isolate from clade A.
19. The method of claim 18 , wherein the clade A primary isolate is 92UG037.8.
20. The method of claim 17 , wherein the clade E primary isolate is 93TH976.17.
21. The method of claim 17 , wherein the wild-type HIV gag protein is a gag protein of a Czm isolate.
22. The method of claim 17 , further comprising isolating immune cells from the human; and testing an immune response of the isolated immune cells in vitro.
23. The method of claim 17 , wherein the protein composition is administered between 4 and 8 weeks after the nucleic acid composition.
24. The method of claim 17 , further comprising testing for a cell-mediated immune response.
25. The method of claim 17 , further comprising testing for a humoral immune response.
26. The method of claim 25 , wherein a neutralizing humoral response is tested.
27. The method of claim 17 , wherein a cell-mediated immune response is induced.
28. The method of claim 17 , wherein a humoral immune response is induced.
29. The method of claim 28 , wherein a neutralizing humoral immune response is induced.
30. The method of claim 17 , wherein the nucleic acid molecules comprise DNA plasmids.
31. The method of claim 17 , wherein one or more of the sets of nucleic acid molecules comprises optimized codons.
32. The method of claim 17 , wherein the set of nucleic acid molecules encoding the gag protein comprises optimized codons.
33. The method of claim 17 , wherein the protein composition is administered with an adjuvant.
34. The method of claim 33 , wherein the adjuvant is QS-21.