US2018346520A1PendingUtilityA1

Methods and compositions for inducing an immune response using conserved element constructs

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Assignee: THE US SECRETARY OF THE DEPARTMENT OF HEALTH ANDPriority: May 13, 2015Filed: May 13, 2016Published: Dec 6, 2018
Est. expiryMay 13, 2035(~8.8 yrs left)· nominal 20-yr term from priority
Inventors:Barbara K. FelberGeorge N. PavlakisJames MullinsAntonio ValentinSiriphan Manocheewa
A61K 9/0019A61K 2039/545A61K 9/0009C12N 2740/16234C07K 14/535C12N 2740/16271C07K 14/005A61K 39/21A61K 39/39C12N 2740/16222C07K 14/161A61K 2039/53A61K 2039/54A61K 2039/572A61K 2039/575C12N 2740/16122A61K 2039/55522C12N 2740/16134C12N 2740/16171A61K 2039/55561C07K 2319/02A61K 39/00
52
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Claims

Abstract

The invention provides methods and compositions for eliciting broad immune responses to HIV envelope proteins. The methods include use of nucleic acids constructs that encode conserved elements of HIV Env to induce immune responses.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of inducing an immune response to a protein of interest, the method comprising:
 priming an immune response to the protein of interest, wherein priming comprises administering at least one nucleic acid construct encoding a conserved element polypeptide, wherein the conserved elements are from the protein of interest and the polypeptide comprises at least three conserved elements, each from 8 to 50 amino acids in length where the conserved elements are joined by non-naturally occurring linkers, with the proviso that a nucleic acid construct encoding the fill-length protein, or a substantially full-length region thereof, is not administered in the priming step;   boosting the immune response to the protein of interest, wherein bolting comprises co-administering (i) a nucleic acid construct encoding the full-length protein, or substantially full-length protein, and (ii) the nucleic acid construct encoding the conserved element polypeptide.   
     
     
         2 . The method of  claim 1 , wherein the boosting step comprises administering the nucleic acid of (i) and the nucleic acid of (ii) at the same time. 
     
     
         3 . The method of  claim 1 or  2 , wherein the nucleic acid constructs are administered intramuscularly by in vivo electroporation. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the priming and boosting steps further comprise administering a second conserved element nucleic acid construct that encodes a second conserved element polypeptide that comprises at least one variant of a conserved element contained in the first conserved element polypeptide, wherein the variant in the second polypeptide differs from the variant in the first polypeptide by 1, 2, 3, 4, or 5 amino acids. 
     
     
         5 . The method of  claim 4 , the first and second conserved element nucleic acid constructs are administered sequentially. 
     
     
         6 . The method of  claim 4 . the first and second conserved element nucleic acid constructs are administered concurrently. 
     
     
         7 . The method of any one of  claims 1  to  6 , wherein the protein of interest is HIV-1 Gag and the conserved elements are from HIV-1 p24 gag . 
     
     
         8 . The method of  claim 7 , wherein one conserved element polypeptide comprises at least 7 conserved elements from different regions of p24 gag ; and each of the conserved elements has a conserved element sequence shown in Table 2. 
     
     
         9 . The method of  claim 8 , wherein one conserved element polypeptide comprises conserved elements that each have a sequence set forth in SEQ ID NOS:26, 27, 28, 29, 30, 31, and 32; and a second conserved element polypeptide comprises conserved elements that each have a sequence set forth in SEQ ID NOS: 33, 34, 35, 36, 37, 38, and 39. 
     
     
         10 . The method of  claim 9 , wherein one Gag conserved element polypeptide comprises the amino acid sequence of SEQ ID NO:40 and the second Gag conserved element polypeptide comprises the amino acid sequence of SEQ ID NO:41. 
     
     
         11 . The method of  claim 9  or  10 , wherein the conserved element polypeptides encoded by the first and second nucleic acid Gag conserved element nucleic acid constructs are each fused to a GM-CSF signal peptide. 
     
     
         12 . The method of any one of  claims 1  to  6 , wherein the protein of interest is an HIV-1 Env sequence. 
     
     
         13 . The method of  claim 12 , wherein one conserved element polypeptide comprises at least 12 conserved elements from different conserved regions of Env of HIV-1 Group M and each of the conserved elements has a conserved element sequence shown in Table 1. 
     
     
         14 . The method of  claim 13 , wherein one conserved element polypeptide comprises conserved elements that each have a sequence set forth in SEQ ID NOS:1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22; and a second conserved element polypeptide comprises conserved elements that each have a sequence set forth in SEQ ID NOS:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23. 
     
     
         15 . The method of  claim 14 . wherein one Env conserved element polypeptide comprises the amino acid sequence of SEQ ID NO 24 and the second Gag conserved element polypeptide comprises the amino acid sequence of SEQ ID NO:25. 
     
     
         16 . The method of  claim 14  or  15 , wherein the conserved element polypeptides encoded by the first and second nucleic acid Env conserved element nucleic acid constructs are each fused to a GM-CSF signal peptide. 
     
     
         17 . The method of any one of  claims 4  to  16 , wherein the first and second nucleic acid conserved element nucleic acid constructs are contained in the same vector. 
     
     
         18 . The method of  claims 4  to  16 , wherein the first and second nucleic acid constructs are contained in different vectors. 
     
     
         19 . The method of any one of  claims 1  to  18 , wherein boosting is performed at least about two weeks after the priming step. 
     
     
         20 . The method of any one of  claim 1  to  19 , wherein the priming step comprises two or three administrations of the one or more conserved element polypeptides, each separated by at least about 2 weeks; and the boosting step comprises two co-administrations, each separated by at least about 2 weeks. 
     
     
         21 . A method of inducing an immune response to HIV Gag in a subject, the method comprising:
 priming an immune response to HIV Gag, wherein priming comprises administering to the subject a CE-encoding expression vector that comprises a nucleic acid sequence encoding p24 Gag CE1 as set forth in Table 2 fused at the N-terminus to a human GM-CSF signal peptide and a nucleic acid sequence encoding p24 Gag CE2 as set forth in Table 2 fused at the N-terminus to a human GM-CSF signal peptide; wherein the subject is not co-administered or has not previously been administered a recombinant nucleic acid construct encoding a full-length or substantiallyl full-length HIV Gag polypeptide;   boosting an immune response to HIV Gag, wherein boosting comprises co-delivering the CE-encoding expression vector with an expression vector that encodes full-length HIV-1 p55 gag  or substantially full-length HIV-1 p55 gag .   
     
     
         22 . The method of  claim 21 , wherein the boosting step is performed about two months after the priming step. 
     
     
         23 . The method of  claim 21  or  22 , wherein the method comprises two or three priming steps, each separated by about two months; and two boost steps, each separated by about two months. 
     
     
         24 . A nucleic acid encoding an immunogenic HIV Env conserved element polypeptide, wherein the HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4; SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and the conserved elements are separated by linkers of 1 to 5 amino acids in length. 
     
     
         25 . The nucleic acid of  claim 24 , wherein the HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22 
     
     
         26 . The nucleic acid of  claim 24 , wherein the HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ NO:8, SEQ ID NO:10, SEQ NO:12, SEQ NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22. 
     
     
         27 . The nucleic acid of  claim 24 ,  25 , or  26 , wherein the HIV Env conserved element polypeptide further comprises a V1V2 variable region sequence. 
     
     
         28 . The nucleic acid of  claim 24 , wherein the HIV Env conserved element polypeptide comprises SEQ ID NO:24. 
     
     
         29 . A nucleic acid encoding an immunogenic HIV Env conserved element polypeptide, wherein the HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23; and the conserved elements are separated by linkers of 1 to 5 amino acids in length. 
     
     
         30 . The nucleic acid of  claim 29 , wherein the HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23. 
     
     
         31 . The nucleic acid of  claim 29 , wherein the HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23. 
     
     
         32 . The nucleic acid of  claim 29 ,  30 , or  31 , further comprising a V1V2 variable region sequence. 
     
     
         33 . The nucleic acid of  claim 29 , wherein the HIV Env conserved element polypeptide comprises SEQ ID NO:25. 
     
     
         34 . The nucleic acid of any one of  claims 24  to  33 , wherein the HIV Env conserved element polypeptide comprises a signal peptide. 
     
     
         35 . The nucleic acid of  claim 34 , wherein the signal peptide is the signal peptide of GM-CSF. 
     
     
         36 . An immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements selected from SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ NO:20, and SEQ ID NO:22, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length 
     
     
         37 . The immunogenic HIV Env conserved element polypeptide of  claim 36 , wherein the polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ NO:1, SEQ NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ NO:8, SEQ NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22 
     
     
         38 . The immunogenic HIV Env conserved element polypeptide of  claim 36 , wherein the polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO: 10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22. 
     
     
         39 . The immunogenic HIV Env conserved element polypeptide of  claim 36 ,  37 , or  38 , wherein the polypeptide further comprises a V1V2 variable region sequence. 
     
     
         40 . The immunogenic HIV Env conserved element polypeptide of  claim 36 , wherein the polypeptide comprises SEQ ID NO:24. 
     
     
         41 . An immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements selected from SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23; wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length. 
     
     
         42 . The immunogenic HIV Env conserved element polypeptide of  claim 41 , wherein the polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23. 
     
     
         43 . The immunogenic HIV Env conserved element polypeptide of  claim 41 , wherein the polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23. 
     
     
         44 . The immunogenic HIV Env conserved element polypeptide of  claim 41 ,  42 , or  43 , wherein the polypeptide further comprises a V1V2 variable region sequence. 
     
     
         45 . The immunogenic HIV Env conserved element polypeptide of  claim 41 , wherein the polypeptide comprises SEQ ID NO:25. 
     
     
         46 . A composition comprising:
 a first nucleic acid construct encoding a first immunogenic HIV Env conserved element polypeptide that comprises at least five conserved elements selected from SEQ ID NO:1, SEQ NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length; and   a second nucleic acid construct encoding a second immunogenic HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length.   
     
     
         47 . The composition of  claim 46 , wherein the first immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1. SEQ NO:2, SEQ ID NO:4, SEQ NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and
 the second immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ 1D NO:15, SEQ SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23.   
     
     
         48 . The composition of  claim 46 , wherein the first immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22. 
     
     
         49 . The composition of  claim 46 , wherein the second immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23. 
     
     
         50 . The composition of  claim 46 , wherein the first immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and
 the second immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ NO:23.   
     
     
         51 . The compositions of any one of  claims 46  to  50 , wherein the first immunogenic HIV Env conserved element polypeptide or the second immunogenic HIV Env conserved element polypeptide; or both the first immunogenic HIV Env conserved element polypeptide and the second immunogenic HIV Env conserved element polypeptide further comprise a V1V2 variable region sequence. 
     
     
         52 . The composition of  claim 46 , wherein the first immunogenic HIV Env conserved element comprises the amino acid sequence of SEQ ID NO:24 and the second immunogenic HIV Env conserved element polypeptide comprises the amino acid sequence of SEQ ID NO:25. 
     
     
         53 . The composition of any one of  claims 46  to  52 , wherein the first nucleic acid and second nucleic acid are contained in separate expression vectors, 
     
     
         54 . The composition of any one of  claims 46  to  52 , wherein the first nucleic acid and second nucleic acid are contained in the same expression vector. 
     
     
         55 . A composition comprising:
 a first immunogenic HIV Env conserved element polypeptide comprising at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ NO:18, SEQ ID NO:20, and SEQ ID NO:22, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length; and   a second immunogenic HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length.   
     
     
         56 . The composition of  claim 55 , wherein the first immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and
 the second immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23.   
     
     
         57 . The composition of  claim 55 , wherein the first immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22. 
     
     
         58 . The composition of  claim 55 , wherein the second immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23. 
     
     
         59 . The composition of  claim 55 , wherein the first immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and
 the second immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23.   
     
     
         60 . The composition of any one of  claims 55  to  59 , wherein the first immunogenic HIV Env conserved element polypeptide or the second immunogenic HIV Env conserved element polypeptide; or both the first immunogenic HIV Env conserved element polypeptide and the second immunogenic HIV Env conserved element polypeptide further comprise a V1V2 variable region sequence. 
     
     
         61 . The composition of  claim 55 , wherein the first immunogenic HIV Env conserved element comprises the amino acid sequence of SEQ ID NO:24 and the second immunogenic HIV Env conserved element polypeptide comprises the amino acid sequence of SEQ NO:25. 
     
     
         62 . A method of inducing an immune response to HIV Env, the method comprising administering a nucleic acid construct of any one of  claims 24  to  35  to a subject or an HIV Env conserved element polypeptide of any one of  claims 36  to  45  to the subject. 
     
     
         63 . A method of inducing an immune response to HIV Env, the method comprising administering:
 a first nucleic acid encoding a first immunogenic HIV Env conserved element polypeptide that comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length; and   a second nucleic acid encoding a second immunogenic HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length.   
     
     
         64 . The method of  claim 63 , wherein:
 the first immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and   the second immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23.   
     
     
         65 . The method of  claim 63 , wherein:
 the first immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ NO:1, SEQ NO:2, SEQ ID NO:4, SEQ NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ NO:22; and   the second immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23.   
     
     
         66 . The method of any one of  claims 63  to  65 , wherein the first immunogenic HIV Env conserved element polypeptide or the second immunogenic HIV Env conserved element polypeptide; or both the first immunogenic HIV Env conserved element polypeptide and the second immunogenic HIV Env conserved element polypeptide further comprise a V1V2 variable region sequence. 
     
     
         67 . The method of  claim 63 , wherein the first immunogenic HIV Env conserved element comprises the amino acid sequence of SEQ ID NO:24 and the second immunogenic HIV Env conserved element polypeptide comprises the amino acid sequence of SEQ ID NO:25. 
     
     
         68 . The method of any one of  claims 63  to  67 , wherein the first nucleic acid and second nucleic acid are contained in separate expression vectors. 
     
     
         69 . The method of any one of  claims 63  to  67 , wherein the first nucleic acid and second nucleic acid are contained in the same expression vector. 
     
     
         70 . The method of any one of  claims 63  to  67 , wherein the first and the second nucleic acids are administered sequentially. 
     
     
         71 . The method of any one of  claims 63  to  67 , wherein the first and second nucleic acids are administered concurrently. 
     
     
         72 . The method of any one of  claims 63  to  71 , wherein a nucleic acid encoding a full-length Env polypeptide, or substantially full-length Env polypeptide, is administered as a boost after the first and the second nucleic acid encoding the first and the second HIV conserved element polypeptides. 
     
     
         73 . The method of any one of  claims 63  to  72 , wherein the nucleic acid constructs are administered intramuscularly by in vivo electroporation. 
     
     
         74 . A method of inducing an immune response to HIV Env, the method comprising administering:
 a first immunogenic HIV Env conserved element polypeptide that comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ NO:22, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length; and   a second immunogenic HIV Env conserved element polypeptide comprises at least five conserved elements selected from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:23, wherein the conserved elements are separated by linkers of 1 to 5 amino acids in length.   
     
     
         75 . The method of  claim 74 , wherein the first immunogenic Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and
 the second immunogenic HIV Env conserved element polypeptide comprises at least six, seven, eight, nine, ten, or eleven conserved elements selected from SEQ NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO.21, and SEQ ID NO:23.   
     
     
         76 . The method of  claim 74 , wherein the first immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, and SEQ ID NO:22; and
 the second immunogenic HIV Env conserved element polypeptide comprises the conserved elements of SEQ ID NO:1, SEQ ID NO:3, SEQ NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ NO:21, and SEQ ID NO:23.   
     
     
         77 . The method of any one of  claims 74  to  76 , wherein the first immunogenic HIV Env conserved element polypeptide or the second immunogenic HIV Env conserved element polypeptide; or both the first immunogenic My Env conserved element polypeptide and the second immunogenic HIV Env conserved element polypeptide further comprise a V1V2 variable region sequence. 
     
     
         78 . The method of  claim 74 , wherein the first immunogenic HIV Env conserved element comprises the amino acid sequence of SEQ ID NO:24 and the second immunogenic HIV Env conserved element polypeptide comprises the amino acid sequence of SEQ ID NO:25. 
     
     
         79 . The method of any one of  claims 74  to  78 , wherein the first and the second immunogenic HIV Env conserved element polypeptides are administered sequentially. 
     
     
         80 . The method of any one of  claims 74  to  78 , wherein the first and the second immunogenic HIV Env conserved element polypeptides are administered concurrently. 
     
     
         81 . The method of any one of  claims 74  to  80 , wherein a full-length Env polypeptide, or substantially fill-length Env polypeptide, is administered after the first and the second second HIV conserved element polypeptides. 
     
     
         82 . An HIV Gag CE polypeptide comprising:
 (a) SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, and/or SEQ NO:37; or   (b) SEQ ID NO:28, SEQ NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ NO:36, and/or SEQ ID NO:38.   
     
     
         83 . An HIV Gag CE polypeptide comprising:
 P24CE8-1, p24CE9-1, p24CE3-1, p24CE10-1, p24CE5-1, p24CE11-1, p24CE6-1, p24CE12-1, p24CE13-1 as shown in  FIG. 23 ; or   P24CE8-1, p24CE9-2, p24CE3-2, p24CE10-21, p24CE5-2, p24CE11-2, p24CE6-2, p24CE12-2, p24CE13-2 as shown in  FIG. 23 .   
     
     
         84 . The method of any one of  claims 62  to  81 , further comprising administering an immunogenic composition to induce an immune response to HIV Gag, wherein the immunogenic composition is an HIV Gag CE polypeptide comprising p24 CE1, CE2, CE3, CE4, CE5, CE6, and CE7 as shown in  FIG. 23 ; or an HIV Gag CE polypeptide of  claim 82  or  83 . 
     
     
         85 . The method of any one of  claims 62  to  81 , further comprising administering an immunogenic composition to induce an immune response to HIV Gag, wherein the method comprises administering an HIV Gag CE polypeptide comprising P24CE8-1, p24CE9-1, p24CE3-1, p24CE10-1, p24CE5-1, p24CE11-1, p24CE6-1, p24CE12-1, p24CE13-1 as shown in  FIGS. 15  and P24CE8-1, p24CE9-2, p24CE3-2, p24CE10-21, p24CE5-2, p24CE11-2, p24CE6-2, p24CE12-2, p24CE13-2 as shown in  FIG. 23 . 
     
     
         86 . A nucleic acid construct encoding an HIV Gag CE polypeptide of  claim 82  or  83 . 
     
     
         87 . The method of  claim 84  or  85 , wherein the HIV Gag CE polypeptide is administered as a nucleic acid that encodes the HIV Gag CE polypeptide.

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