Compositions and methods to treat AIDS
Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV are disclosed. The compositions and methods described herein are for the use of a nucleic acid composition that encodes one or more different HIV envelope glycoproteins. The synthetic, codon-optimized 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 polypeptide compositions for inducing an immune response against HIV are also disclosed. Methods for using the polypeptide compositions before, at the same time as, and/or after 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 subject, the method comprising administering to the subject at least one of the following:
a nucleic acid composition comprising at least two different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5 or 7; and
a polypeptide composition comprising at least two different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5 or 7;
wherein the nucleic acid composition and/or the polypeptide composition are administered in an amount sufficient to induce an immune response against HIV or an HIV epitope in the subject.
2. The method of claim 1 , wherein the nucleic acid composition is administered before the polypeptide composition.
3. The method of claim 1 , wherein the nucleic acid composition is administered three times before the polypeptide composition is administered two times.
4. The method of claim 1 , wherein the polypeptide composition is administered before the nucleic acid composition.
5. The method of claim 1 , wherein the nucleic acid composition is administered at the same time as the polypeptide composition.
6. The method of claim 1 , wherein a neutralizing humoral immune response is induced.
7. The method of claim 1 , wherein a cell-mediated immune response is induced.
8. The method of claim 1 , wherein the subject is human.
9. The method of claim 1 , wherein the method further comprises administering a therapeutic agent for HIV infection.
10. The method of claim 9 , wherein the therapeutic agent for HIV infection is a nucleoside reverse transcriptase inhibitor, a non-nucleoside reverse transcriptase inhibitor, or an HIV protease inhibitor.
11. The method of claim 1 , wherein the synthetic, codon-optimized nucleic acid molecule comprises a nucleotide sequence that has at least 92% identity to the nucleotide sequence of SEQ ID NO:5 or 7.
12. The method of claim 1 , wherein the synthetic, codon-optimized nucleic acid molecule comprises a nucleotide sequence that has at least 95% identity to the nucleotide sequence of SEQ ID NO:5 or 7.
13. The method of claim 1 , wherein the synthetic, codon-optimized nucleic acid molecule comprises a nucleotide sequence that has at least 97% identity to the nucleotide sequence of SEQ ID NO:5 or 7.
14. The method of claim 1 , wherein the synthetic, codon-optimized nucleic acid molecule comprises a nucleotide sequence that has at least 99% identity to the nucleotide sequence of SEQ ID NO:5 or 7.
15. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least two different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5; and
a polypeptide composition comprising at least two different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5.
16. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least three different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5; and
a polypeptide composition comprising at least three different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least three of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5.
17. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least four different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5; and
a polypeptide composition comprising at least four different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5.
18. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least two different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7; and
a polypeptide composition comprising at least two different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7.
19. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least three different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7; and
a polypeptide composition comprising at least three different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least three of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7.
20. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least four different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7; and
a polypeptide composition comprising at least four different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:1, 3, 5, 7, and 9, wherein one of the synthetic, codon-optimized nucleic acid molecules comprises a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7.
21. The method of claim 1 , wherein the method comprises administering to the subject at least one of the following:
a nucleic acid composition comprising at least two different synthetic, codon-optimized nucleic acid molecules comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein two of the synthetic, codon-optimized nucleic acid molecules comprise a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5 and a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7; and
a polypeptide composition comprising at least two different isolated polypeptides encoded by a synthetic, codon-optimized nucleic acid molecule comprising a nucleotide sequence that has at least 90% identity to the nucleotide sequence of at least two of SEQ ID NO:1, 3, 5, 7, and 9, wherein two of the synthetic, codon-optimized nucleic acid molecules comprise a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:5 and a nucleotide sequence that has at least 90% identity to the nucleotide sequence of SEQ ID NO:7.