Recombinant HIV Env polypeptides and their uses

Inventors: Dennis R. Burton (La Jolla, CA); Raiees Andrabi (New York, NY)

Assignees: INTERNATIONAL AIDS VACCINE INITIATIVE; THE SCRIPPS RESEARCH INSTITUTE

C07K14/005 A61K39/21 C12N2740/16122 C12N2740/16134

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Quick Facts

Patent No.: US 12679869
App. No.: 17/299,062
Granted: Jul 14, 2026
Kind: B2

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Abstract

The present disclosure relates to recombinant HIV Env polypeptides and their use in the treatment and prevention of HIV/AIDS.

Claims (30)

1 . An engineered or non-naturally occurring HIV Env polypeptide, wherein

a) the engineered or non-naturally occurring HIV Env polypeptide is missing glycan sequons at N156 and N130 and has one or more basic residues at positions 168 to 171, wherein the HIV Env polypeptide; or

b) the engineered or non-naturally occurring HIV Env polypeptide is an engineered or non-naturally occurring ZM233 HIV Env polypeptide missing glycan sequons at N156 and N130,

wherein the HIV Env polypeptide positions correspond to the HXB2 reference (SEQ ID NO: 1).

2 . The engineered or non-naturally occurring HIV Env polypeptide of claim 1 , which binds to an HIV broadly neutralizing antibody (bnAb) directed to the V2 apex region of HIV envelope.

3 . The engineered or non-naturally occurring HIV ENV polypeptide of claim 1 , which is a chimeric HIV Env polypeptide comprising an HIV Env polypeptide backbone and the V1V2 region of the ZM233 HIV Env polypeptide.

4 . The engineered or non-naturally occurring HIV Env polypeptide of claim 3 , wherein the V1V2 region of the ZM233 HIV Env polypeptide comprises the amino acid sequence of SEQ ID NO: 9.

5 . The engineered or non-naturally occurring HIV Env polypeptide of claim 3 , wherein the HIV Env polypeptide backbone comprises a BG505, ZM197, or CFR250 backbone.

6 . The engineered or non-naturally occurring HIV Env polypeptide of claim 1 , which is a chimeric HIV Env polypeptide comprising an HIV Env polypeptide backbone and the amino acid residues of the ZM233 HIV Env polypeptide corresponding to positions about 131 to about 196.

7 . The engineered or non-naturally occurring HIV Env polypeptide of claim 6 , wherein the HIV Env polypeptide backbone comprises a BG505, ZM197, or CFR250 backbone.

8 . The engineered or non-naturally occurring HIV Env polypeptide of claim 1 , which comprises a complex of gp120 and gp41 or a stabilized trimer, optionally wherein the trimer is a SOSIP, NFL, or UFO trimer.

9 . The engineered or non-naturally occurring HIV Env polypeptide of claim 1 , which comprises a V2 apex epitope of ZM233 Env.

10 . The HIV Env polypeptide of claim 9 ,

(a) which comprises basic amino acid substitutions at positions 168 to 171, wherein the HIV Env polypeptide positions correspond to the HXB2 reference,

(b) wherein the V2 apex region of positions 156 to 175 comprises one glycan and four consecutive basic amino acids, or

11 . The engineered or non-naturally occurring HIV Env polypeptide of claim 1 comprising the amino acid sequence of I-C-X 1 -F-N-X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -V-N-V-L (SEQ ID NO: 10) at positions 156 to 175, wherein X 1 comprises S, T, N, or F; X 2 comprises I, V, T, Q, or M; X 3 comprises S or T; X 4 comprises S or T; X 5 comprises S, E, or G; X 6 comprises I, L, or V; X 7 comprises K or R; X 8 comprises G or D; X 9 comprises K, R, E, or Q; X 10 comprises K, R, E, or Q; X 11 comprises K, R, E, or Q; and X 12 comprises K, E, or Q.

12 . The engineered or non-naturally occurring HIV Env polypeptide of claim 11 , wherein at least three of X9, X10, X11, and X12 comprise basic amino acid residues, all of X9, X10, X11, and X12 comprise basic amino acid residues, or X9, X10, X11, and X12 comprise K.

13 . A nucleic acid molecule encoding the engineered or non-naturally occurring HIV Env polypeptide of claim 1 .

14 . A vector comprising a regulatory element operable in a eukaryotic cell operably linked to the nucleic acid molecule of claim 13 .

15 . The vector of claim 14 , wherein the vector comprises AAV.

16 . A method of eliciting an immune response or stimulating of a broadly neutralizing HIV antibody (bnAb) in a mammal comprising administering

a) at least one engineered or non-naturally occurring HIV Env polypeptide of claim 1 ;

b) a nucleic acid molecule encoding at least one engineered or non-naturally occurring HIV Env polypeptide of claim 1 ; or

c) a vector comprising a nucleic acid molecule encoding at least one engineered or non-naturally occurring HIV Env polypeptide of claim 1 .

17 . The method of claim 16 , wherein the engineered or non-naturally occurring HIV Env polypeptide comprises a V2 apex epitope of ZM233 trimer.

18 . A chimeric HIV Env polypeptide comprising an HIV Env polypeptide backbone and

a) the V1V2 region of the ZM233 HIV Env polypeptide; or

b) the amino acid residues of the ZM233 HIV Env polypeptide corresponding to positions about 131 to about 196, wherein the HIV Env polypeptide positions correspond to the HXB2 reference.

19 . An HIV Env polypeptide comprising the amino acid sequence of SEQ ID NO: 6, 7, or 8.