Methods and compositions for inducing an immune response using conserved element constructs
AssigneesThe United States of America, as represented by the Secretary, Department of Health and, Human Services, University of Washington
InventorsBarbara K. Felber, George N. Pavlakis, James I. Mullins, Antonio Valentin, Siriphan Manocheewa
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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.
Claims87
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.
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 p24GagCE1 as set forth in Table 2 fused at the N-terminus to a human GM-CSF signal peptide and a nucleic acid sequence encoding p24GagCE2 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 p55gag or substantially full-length HIV-1 p55gag.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
Dependencies are inferred from the claim text.