Stabilized human immunodeficiency virus (HIV) clade C envelope (Env) trimer vaccines and methods of using same
The invention features stabilized human immunodeficiency virus (H IV) clade C envelope (Env) trimers. The invention also features vaccines, nucleic acids, and vectors to deliver and/or facilitate production of the stabilized HIV clade C Env trimers. In addition, the invention features methods of making and using the stabilized HIV clade C Env trimers of the invention.
1. An immunogenic composition comprising a gp140 polypeptide, wherein the polypeptide comprises:
(a) at least 90% sequence identity over the entire length of SEQ ID NO: 1 and has a V1/V2 epitope corresponding to amino acids 166-183 of SEQ ID NO: 1 and a V3 epitope corresponding to amino acids 342-348 of SEQ ID NO: 1;
(b) at least 90% sequence identity over the entire length of SEQ ID NO: 2 and has a V1/V2 epitope corresponding to amino acids 155-172 of SEQ ID NO: 2 and a V3 epitope corresponding to amino acids 330-335 of SEQ ID NO: 2; or
(c) at least 90% sequence identity over the entire length of SEQ ID NO: 3 and has a V1/V2 epitope corresponding to amino acids 150-167 of SEQ ID NO: 3 and a V3 epitope corresponding to amino acids 328-334 of SEQ ID NO: 3;
wherein the polypeptide is capable of inducing a neutralizing antibody response.
2. The immunogenic composition of claim 1 comprising a stabilized trimer of the gp140 polypeptide, wherein each of the gp140 polypeptides of the stabilized trimer has the same amino acid sequence.
3. The immunogenic composition of claim 2 comprising at least two different stabilized trimers.
4. The immunogenic composition of claim 2 , wherein the amino acid sequence of each of the gp140 polypeptides of the stabilized trimer has at least 95% sequence identity over the entire length of any one of SEQ ID NOs: 1, 2, and 3.
5. The immunogenic composition of claim 2 , wherein said composition further comprises a stabilized C97ZA012 gp140 trimer.
6. The immunogenic composition of claim 1 , further comprising: (i) a pharmaceutically acceptable carrier, excipient, or diluent, and/or (ii) an adjuvant.
7. A kit comprising:
(a) the immunogenic composition of claim 1 ;
(b) a pharmaceutically acceptable carrier, excipient, or diluent; and
(c) instructions for use thereof, wherein said kit optionally includes an adjuvant.
8. The immunogenic composition of claim 1 , wherein the amino acid sequence of the gp140 polypeptide has at least 95% sequence identity over the entire length of SEQ ID NO: 1, 2, or 3.
9. The immunogenic composition of claim 8 , wherein the amino acid sequence of the gp140 polypeptide comprises the amino acid sequence of SEQ ID NO: 1, 2, or 3.
10. The immunogenic composition of claim 4 , wherein the amino acid sequence of each of the gp140 polypeptides of the stabilized trimer has at least 99% sequence identity-over the entire length of any one of SEQ ID NOs: 1, 2, and 3.
11. The immunogenic composition of claim 10 , wherein each of the gp140 polypeptides of the stabilized trimer comprises the amino acid sequence of any one of SEQ ID NOs: 1, 2, and 3.
12. The immunogenic composition of claim 8 , wherein the amino acid sequence of the gp140 polypeptide has at least 99% sequence identity over the entire length of SEQ ID NO: 1, 2, or 3.
13. The immunogenic composition of claim 1 , wherein the polypeptide of (a) further comprises one or more of amino acids 121-128, 287-295, 375-386, 434-441, 462-468, or 478-486 of SEQ ID NO: 1.
14. The immunogenic composition of claim 1 , wherein the polypeptide of (b) further comprises one or more of amino acids 121-128, 275-283, 361-372, 408-415, 436-442, or 455-463 of SEQ ID NO: 2.
15. The immunogenic composition of claim 1 , wherein the polypeptide of (c) further comprises one or more of amino acids 121-128, 273-281, 361-372, 419-426, 447-453, or 466-474 of SEQ ID NO: 3.
16. The immunogenic composition of claim 1 , wherein the polypeptide of (a) further comprises amino acids 121-128, 287-295, 375-386, 434-441, 462-468, and 478-486 of SEQ ID NO: 1.
17. The immunogenic composition of claim 1 , wherein the polypeptide of (b) further comprises amino acids 121-128, 275-283, 361-372, 408-415, 436-442, and 455-463 of SEQ ID NO: 2.
18. The immunogenic composition of claim 1 , wherein the polypeptide of (c) further comprises amino acids 121-128, 273-281, 361-372, 419-426, 447-453, and 466-474 of SEQ ID NO: 3.