IP Library › Granted Patent US 12,551,547

Granted Patent B2

US 12,551,547 · App. 17/437,470 · Granted Feb 17, 2026

Highly networked immunogen composition

Inventors: Bruce D. Walker (Nahant, MA); Gaurav D. Gaiha (Somerville, MA); Elizabeth Rossin (Charlestown, MA)

Assignees: The General Hospital Corporation; Massachusetts Eye and Ear Infirmary

A61K39/21 A61P31/18 A61P37/04

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Quick Facts

Patent No.: US 12,551,547
App. No.: 17/437,470
Granted: Feb 17, 2026
Kind: B2

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Abstract

A method of preventing or treating HIV in a subject includes selecting two or more HIV CTL epitopes from an HIV proteome that have a network score that meets a threshold value. The network score for a given epitope can be determined by generating at least one network representing protein structure, calculating a set of network parameters, combining the network parameters to determine a network score for each amino acid residue in the protein structure, generating a network score for each of a plurality of epitopes as a weighted linear combination of the amino acid residues of the epitopes, and selecting two or more epitopes according to their network score. An effective amount of a T cell immunogen composition and a pharmaceutically acceptable carrier is administered to the subject. The T cell immunogen composition includes the two or more selected HIV CTL epitopes.

Claims (32)

1 . A multi-epitope T cell immunogen composition comprising two highly networked human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL) epitopes, wherein the two highly networked HIV CTL epitopes are human leukocyte antigen (HLA)-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO:201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO:202), or wherein the amino acid sequences of the highly networked HIV CTL epitopes have at least about 75% to about 99% homology to the amino acid sequences of HLA-B*57 KF11 and HLA-B*57 TW10.

2 . A multi-epitope T cell immunogen composition comprising two or more highly networked HIV CTL epitopes, wherein the two highly networked HIV CTL epitopes are HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO:201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO:202), and further comprising at least ten HIV CTL epitopes, wherein the ten HIV CTL epitopes are HLA-A*11 AVDLSHFLK (AK9) (SEQ ID NO: 40) and highly networked epitopes restricted by HLA-A*02, HLA-A*03, HLA-A*11 or HLA-B*07 are selected from the group consisting of HLA-A*02 YVDRFYKTL (YL9) (SEQ ID NO: 23), HLA-A*03 GIPHPAFLK (GK9) (SEQ ID NO: 377), HLA-B*07 TPQDLNTML (TL9) (SEQ ID NO: 97), HLA-A*11 ACQGVGGPGHK (AK11) (SEQ ID NO: 43), HLA-A*02 VL9 VIYQYMDDL (VL9) (SEQ ID NO: 13), HLA-A*02 KLTPLCVTL (KL9) (SEQ ID NO: 11), HLA-B*07 SPRTLNAWV (SV9) (SEQ ID NO: 88), HLA-A*02 PLTFGWCYKL (PL10) (SEQ ID NO: 10), and B*07 TPGPGVRYPL (TL10) (SEQ ID NO: 98), or wherein the amino acid sequences of the HIV CTL epitopes have at least about 75% to about 99% homology to the amino acid sequences of HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO:201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO:202), HLA-A*02 YVDRFYKTL (YL9) (SEQ ID NO: 23), HLA-A*03 GIPHPAFLK (GK9) (SEQ ID NO: 377), HLA-B*07 TPQDLNTML (TL9) (SEQ ID NO: 97), HLA-A*11 ACQGVGGPGHK (AK11) (SEQ ID NO: 43), HLA-A*02 VL9 VIYQYMDDL (VL9) (SEQ ID NO: 13), HLA-A*11 AVDLSHFLK (AK9) (SEQ ID NO: 40), HLA-A*02 KLTPLCVTL (KL9) (SEQ ID NO: 11), HLA-B*07 SPRTLNAWV (SV9) (SEQ ID NO: 88), HLA-A*02 PLTFGWCYKL (PL10) (SEQ ID NO: 10), and B*07 TPGPGVRYPL (TL10) (SEQ ID NO: 98).

3 . A multi-epitope T cell immunogen composition comprising two highly networked HIV CTL epitopes HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO:201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO:202), or amino acid sequences having at least about 75% to about 99% homology to the amino acid sequences of HLA-B*57 KF11 of and HLA-B*57 TW10 and further comprising two highly networked HIV CTL epitopes restricted by HLA-E*101 and HLA-E*103, wherein the two highly networked HIV CTL epitopes are selected from HLA-E*101/E*103 SALSEGATP (SEQ ID NO: 261), HLA-E*101/E*103 RMYSPTSIL (SEQ ID NO: 262), HLA-E*101/E*103 AISPRTLNA (SEQ ID NO: 265), HLA-E*101/E*103 STLQEQIGW (SEQ ID NO: 266), HLA-E*101/E*103 HQAISPRTL (SEQ ID NO: 270), and HLA-E*101/E*103 VGGHQAAMQ (SEQ ID NO: 271).

4 . A method of preventing HIV infection in a subject, the method comprising:

administering to the subject a prophylactically effective amount of the multi-epitope T cell immunogen composition of claim 1 , and a pharmaceutically acceptable carrier, thereby preventing HIV infection in the subject.

5 . An RNA vector comprising a multi-epitope T cell immunogen, wherein the vector comprises a sequence comprising two or more highly networked HIV CTL epitopes, wherein the two or more highly networked HIV CTL epitopes each have a network score from 3.04 to 9.05.

6 . The RNA vector of claim 5 , wherein the two or more highly networked HIV CTL epitopes each have a network score of at least 3.06.

7 . The RNA vector of claim 5 , wherein, for each of the highly networked HIV CTL epitopes, the RNA vector comprises an endoplasmic reticulum insertion signal sequence (ERISS).

8 . The RNA vector of claim 5 , wherein, for each of the highly networked HIV CTL epitopes, the RNA vector comprises an enzyme cleavage site sequence.

9 . The RNA vector of claim 8 , wherein the enzyme cleavage site is a furin cleavage site sequence.

10 . The RNA vector of claim 5 , wherein the sequences comprising the two or more highly networked HIV CTL epitopes are linked by a linker sequence.

11 . The RNA vector of claim 10 , wherein the linker sequence comprises Alanine and Tyrosine.

12 . The RNA vector of claim 5 , wherein two of the highly networked HIV CTL epitopes are HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO:201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO:202), or

wherein the two or more highly networked HIV CTL epitopes are selected from the group consisting of HLA-A*01/A*29/B*35/B*57 YFPDWQNYT (SEQ ID NO: 2), HLA-A*02 YVDRFYKTL (SEQ ID NO: 23), HLA-A*02 PLTFGWCYKL (SEQ ID NO: 10), HLA-A*02 KLTPLCVTL (SEQ ID NO: 11), HLA-A*02 VIYQYMDDL (SEQ ID NO: 13), HLA-A*02 LVGPTPVNI (SEQ ID NO: 12), HLA-A*03 GIPHPAGLK (SEQ ID NO: 24), HLA-A*11 ACQGVGGPGHK (SEQ ID NO: 43), HLA-A*24 RDYVDRFYKTL (SEQ ID NO: 54), HLA-A*26 EVIPMFSAL (SEQ ID NO: 59), HLA-B*07 TPQDLNTML (SEQ ID NO: 97), HLA-B*07 SPRTLNAWV (SEQ ID NO: 88), HLA-B*07 TPGPGVRYPL (SEQ ID NO: 98), HLA-B*14 VRMYSPVSI (SEQ ID NO: 216), HLA-B*14 DRFYKTLRA (SEQ ID NO: 112), HLA-B*14 IRYQYNVL (SEQ ID NO: 111), HLA-B*1501 GLNKIVRMY (SEQ ID NO: 116), HLA-B*1510/B*3901 GHQAAMQML (SEQ ID NO: 130), HLA-B*18/B*53 YPLTFGWCY (SEQ ID NO: 135), HLA-B*27 TRYPLTFGW (SEQ ID NO: 75), HLA-B*27 KRKGGIGGY (SEQ ID NO: 140), HLA-B*27 KRWIILGLNK (SEQ ID NO: 141), HLA-B*40 SEGATPQDL (SEQ ID NO: 161), HLA-B*40 GERIVDII (SEQ ID NO: 168), HLA-B*44 EEKAFSPEV (SEQ ID NO: 178), HLA-B*44 AEQASQDVKNW (SEQ ID NO: 176), HLA-B*49 TWEAWWTEYW (SEQ ID NO: 182), HLA-B*51/Cw*03/Cw*15 RAIEAQQHL (SEQ ID NO: 183), HLA-B*53/B*57 QASQEVKNW (SEQ ID NO: 189), HLA-B*57 IAMESIVIW (SEQ ID NO: 195), HLA-B*57 ISPRTLNAW (SEQ ID NO: 204), HLA-B*57 KAFSPEVIPMF (SEQ ID NO: 201), HLA-B*57 TSTLQEQIGW (SEQ ID NO: 202), HLA-B*81 TPVNIIGRNML (SEQ ID NO: 240), and HLA-Cw*08 IVTDSQYAL (SEQ ID NO: 246), or

wherein the two or more highly networked HIV CTL epitopes are selected from the group consisting of HLA-E*101/HLA-E*103 SALSEGATP (SEQ ID NO: 261), HLA-E*101/HLA-E*103 VGGHQAAMQ (SEQ ID NO: 271), HLA-E*101/HLA-E*103 HQAISPRTL (SEQ ID NO: 270), HLA-E*101/HLA-E*103 RIRTWKSLV (SEQ ID NO: 264), HLA-E*101/HLA-E*103 RMYSPTSIL (SEQ ID NO: 262), HLA-E*101/HLA-E*103 AISPRTLNA (SEQ ID NO: 265), and HLA-E*101/HLA-E*103 STLQEQIGW (SEQ ID NO: 266), or

wherein the two or more highly networked HIV CTL epitopes are selected from the group consisting of HLA-A*02 YVDRFYKTL (SEQ ID NO: 23), HLA-A*02 PLTFGWCYKL (SEQ ID NO: 10), HLA-A*02 KLTPLCVTL (SEQ ID NO: 11), HLA-A*02 VIYQYMDDL (SEQ ID NO: 13), HLA-A*02 LVGPTPVNI (SEQ ID NO: 12), HLA-A*03 GIPHPAGLK (SEQ ID NO: 24), HLA-B*07 TPQDLNTML (SEQ ID NO: 97), HLA-B*07 SPRTLNAWV (SEQ ID NO: 88), HLA-B*07 TPGPGVRYPL (SEQ ID NO: 98), HLA-B*40 SEGATPQDL (SEQ ID NO: 161), HLA-E*101/HLA-E*103 SALSEGATP (SEQ ID NO: 261), HLA-E*101/HLA-E*103 VGGHQAAMQ (SEQ ID NO: 271), HLA-E*101/HLA-E*103 HQAISPRTL (SEQ ID NO: 270), HLA-E*101/HLA-E*103 RMYSPTSIL (SEQ ID NO: 262), HLA-E*101/HLA-E*103 AISPRTLNA (SEQ ID NO: 265), and HLA-E*101/HLA-E*103 STLQEQIGW (SEQ ID NO: 266), or

13 . The RNA vector of claim 5 , wherein the vector comprises sequences comprising highly networked HIV CTL epitopes having at least about 75% to about 99% homology to epitopes HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO:201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO:202), or

wherein the vector comprises sequences comprising highly networked HIV CTL epitopes having at least 65% to about 99% homology to epitopes HLA-A*01/A*29/B*35/B*57 YFPDWQNYT (SEQ ID NO: 2), HLA-A*02 YVDRFYKTL (SEQ ID NO: 23), HLA-A*02 PLTFGWCYKL (SEQ ID NO: 10), HLA-A*02 KLTPLCVTL (SEQ ID NO: 11), HLA-A*02 VIYQYMDDL (SEQ ID NO: 13), HLA-A*02 LVGPTPVNI (SEQ ID NO: 12), HLA-A*03 GIPHPAGLK (SEQ ID NO: 24), HLA-A*11 ACQGVGGPGHK (SEQ ID NO: 43), HLA-A*24 RDYVDRFYKTL (SEQ ID NO: 54), HLA-A*26 EVIPMFSAL (SEQ ID NO: 59), HLA-B*07 TPQDLNTML (SEQ ID NO: 97), HLA-B*07 SPRTLNAWV (SEQ ID NO: 88), HLA-B*07 TPGPGVRYPL (SEQ ID NO: 98), HLA-B*14 VRMYSPVSI (SEQ ID NO: 216), HLA-B*14 DRFYKTLRA (SEQ ID NO: 112), HLA-B*14 IRYQYNVL (SEQ ID NO: 111), HLA-B*1501 GLNKIVRMY (SEQ ID NO: 116), HLA-B*1510/B*3901 GHQAAMQML (SEQ ID NO: 130), HLA-B*18/B*53 YPLTFGWCY (SEQ ID NO: 135), HLA-B*27 TRYPLTFGW (SEQ ID NO: 75), HLA-B*27 KRKGGIGGY (SEQ ID NO: 140), HLA-B*27 KRWIILGLNK (SEQ ID NO: 141), HLA-B*40 SEGATPQDL (SEQ ID NO: 161), HLA-B*40 GERIVDII (SEQ ID NO: 168), HLA-B*44 EEKAFSPEV (SEQ ID NO: 178), HLA-B*44 AEQASQDVKNW (SEQ ID NO: 176), HLA-B*49 TWEAWWTEYW (SEQ ID NO: 182), HLA-B*51/Cw*03/Cw*15 RAIEAQQHL (SEQ ID NO: 183), HLA-B*53/B*57 QASQEVKNW (SEQ ID NO: 189), HLA-B*57 IAMESIVIW (SEQ ID NO: 195), HLA-B*57 ISPRTLNAW (SEQ ID NO: 204), HLA-B*57 KAFSPEVIPMF (SEQ ID NO: 201), HLA-B*57 TSTLQEQIGW (SEQ ID NO: 202), HLA-B*81 TPVNIIGRNML (SEQ ID NO: 240), and HLA-Cw*08 IVTDSQYAL (SEQ ID NO: 246), or

wherein the vector comprises sequences comprising highly networked HIV CTL epitopes having at least 65% to about 99% homology to epitopes HLA-E*101/HLA-E*103 SALSEGATP (SEQ ID NO: 261), HLA-E*101/HLA-E*103 VGGHQAAMQ (SEQ ID NO: 271), HLA-E*101/HLA-E*103 HQAISPRTL (SEQ ID NO: 270), HLA-E*101/HLA-E*103 RMYSPTSIL (SEQ ID NO: 262), HLA-E*101/HLA-E*103 AISPRTLNA (SEQ ID NO: 265), HLA-E*101/HLA-E*103 STLQEQIGW (SEQ ID NO: 266), or

wherein the vector comprises sequences comprising highly networked HIV CTL epitopes having at least 65% to about 99% homology to epitopes HLA-A*02 YVDRFYKTL (SEQ ID NO: 23), HLA-A*02 PLTFGWCYKL (SEQ ID NO: 10), HLA-A*02 KLTPLCVTL (SEQ ID NO: 11), HLA-A*02 VIYQYMDDL (SEQ ID NO: 13), HLA-A*02 LVGPTPVNI (SEQ ID NO: 12), HLA-A*03 GIPHPAGLK (SEQ ID NO: 24), HLA-B*07 TPQDLNTML (SEQ ID NO: 97), HLA-B*07 SPRTLNAWV (SEQ ID NO: 88), HLA-B*07 TPGPGVRYPL (SEQ ID NO: 98), HLA-B*40 SEGATPQDL (SEQ ID NO: 161), HLA-E*101/HLA-E*103 SALSEGATP (SEQ ID NO: 261), HLA-E*101/HLA-E*103 VGGHQAAMQ (SEQ ID NO: 271), HLA-E*101/HLA-E*103 HQAISPRTL (SEQ ID NO: 270), HLA-E*101/HLA-E*103 RMYSPTSIL (SEQ ID NO: 262), HLA-E*101/HLA-E*103 AISPRTLNA (SEQ ID NO: 265), and HLA-E*101/HLA-E*103 STLQEQIGW (SEQ ID NO: 266), or

14 . A pharmaceutical composition comprising the vector of claim 5 .

15 . A method of preventing or treating an HIV infection in a subject, said method comprising administering the vector of claim 5 to the subject, thereby preventing or treating the HIV infection in the subject.

16 . A viral vector comprising a multi-epitope T cell immunogen, wherein the vector comprises a sequence comprising two or more highly networked HIV CTL epitopes, wherein the two or more highly networked HIV CTL epitopes each have a network score from 3.04 to 9.05, and wherein the viral vector is selected from the group consisting of a human adenovirus, a rhesus adenovirus, adeno-associated virus, Gorilla adenovirus, modified Ankara virus, herpesvirus, and a cytomegalovirus (CMV) viral vector.

17 . The RNA vector of claim 5 , wherein the RNA sequence is an mRNA, replicon RNA or self-amplifying RNA.

18 . The RNA vector of claim 5 , comprising HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO: 201) and HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO: 202) and further comprising at least ten highly networked HIV CTL epitopes restricted by HLA-A*02, HLA-A*03, HLA-A*11 or HLA-B*07, wherein the ten highly networked HIV CTL epitopes restricted by HLA-A*02, HLA-A*03, HLA-A*11 or HLA-B*07 are HLA-A*02 YVDRFYKTL (SEQ ID NO: 23), HLA-A*02 PLTFGWCYKL (SEQ ID NO: 10), HLA-A*02 KLTPLCVTL (SEQ ID NO: 11), HLA-A*02 VIYQYMDDL (SEQ ID NO: 13), HLA-A*02 LVGPTPVNI (SEQ ID NO: 12), HLA-A*03 GIPHPAGLK (SEQ ID NO: 24), HLA-A*11 ACQGVGGPGHK (SEQ ID NO: 43), HLA-B*07 TPQDLNTML (SEQ ID NO: 97), HLA-B*07 SPRTLNAWV (SEQ ID NO: 88), and HLA-B*07 TPGPGVRYPL (SEQ ID NO: 98) or

wherein the amino acid sequences of the highly networked HIV CTL epitopes have at least about 65% to about 99% homology to the amino acid sequences of HLA-B*57 KAFSPEVIPMF (KF11) (SEQ ID NO: 201), HLA-B*57 TSTLQEQIGW (TW10) (SEQ ID NO: 202), HLA-A*02 YVDRFYKTL (YL9) (SEQ ID NO: 23), HLA-A*03 GIPHPAFLK (GK9) (SEQ ID NO: 377), HLA-B*07 TPQDLNTML (TL9) (SEQ ID NO: 97), HLA-A*11 ACQGVGGPGHK (AK11) (SEQ ID NO: 43), HLA-A*02 VL9 VIYQYMDDL (VL9) (SEQ ID NO: 13), HLA-A*02 LVGPTPVNI (SEQ ID NO: 12), HLA-A*11 AVDLSHFLK (AK9) (SEQ ID NO: 40), HLA-A*02 KLTPLCVTL (KL9) (SEQ ID NO: 11), HLA-B*07 SPRTLNAWV (SV9) (SEQ ID NO:88), HLA-A*02 PLTFGWCYKL (PL10) (SEQ ID NO: 10), and B*07 TPGPGVRYPL (SEQ ID NO: 98).

19 . A method of preventing HIV infection in a subject, the method comprising administering to the subject a prophylactically effective amount of the multi-epitope T cell immunogen composition of claim 2 .

20 . A method of preventing HIV infection in a subject, the method comprising administering to the subject a prophylactically effective amount of the multi-epitope T cell immunogen composition of claim 3 .

Assignments (4)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2022

From: WALKER, BRUCE D.

To: HOWARD HUGHES MEDICAL INSTITUTE

Reel/Frame 060134/0517 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2022

From: HOWARD HUGHES MEDICAL INSTITUTE

To: THE GENERAL HOSPITAL CORPORATION

Reel/Frame 060134/0525 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2022

From: GAIHA, GAURAV

To: THE GENERAL HOSPITAL CORPORATION

Reel/Frame 060134/0534 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2022

From: ROSSIN, ELIZABETH

To: MASSACHUSETTS EYE AND EAR INFIRMARY

Reel/Frame 060134/0558 →

Continuity (2)

Provisional Application 62817094 · Mar 12, 2019

Related Publication 20220323570A1 · Oct 13, 2022

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