SARS-CoV-2 epitope-targeted peptide immunostimulants

Patent metadata

Field	Value
Publication number	US-12209142-B2
Application number	US-202117336276-A
Country	US
Kind code	B2
Filing date	Jun 1, 2021
Priority date	May 29, 2020
Publication date	Jan 28, 2025
Grant date	Jan 28, 2025

Abstract

Disclosed are compounds, compositions, and methods relating to epitope-targeted immunostimulants (EPIs), which comprise a synthetic peptide ligand and an antibody-recruiting moiety. The peptide ligand binds an epitope on a target and the antibody-recruiting moiety recruits antibodies to the target when the EPI is bound to the epitope on the target. Also disclosed are compositions comprising any of the disclosed EPIs. Also disclosed are methods of stimulating an immune reaction to a microorganism or other pathogen in a subject where an EPI is administered to the subject. Also disclosed are methods of identifying the peptide ligand by using multi-omic analysis.

First claim

We claim:

1. An epitope-targeted immunostimulant (EPI) comprising a synthetic peptide ligand conjugated or coupled to an antibody-recruiting moiety,
wherein:
the synthetic peptide ligand has affinity for an epitope on a SARS-CoV-2 protein exposed on a surface of a target,
the antibody-recruiting moiety recruits antibodies to the target when the EPI is bound to the epitope on the target, and
the synthetic peptide ligand comprises the amino acid sequence tGkrw (SEQ ID NO:80), tGarn (SEQ ID NO:81), GGarn (SEQ ID NO:82), ytGak (SEQ ID NO:83), ttyre (SEQ ID NO: 84), sdyre (SEQ ID NO:85), nyrne (SEQ ID NO:86), rynes (SEQ ID NO:87), yrns (SEQ ID NO: 88), vnyks (SEQ ID NO: 89), vnfth (SEQ ID NO:90), tkhyv (SEQ ID NO:91), ykhvd (SEQ ID NO: 92), wkGpa (SEQ ID NO: 93), ytprs (SEQ ID NO:94), ytpen (SEQ ID NO:95), ydrsd (SEQ ID NO:96), refev (SEQ ID NO:97), Innkl (SEQ ID NO:98), nnpdh (SEQ ID NO:99), npshf (SEQ ID NO: 100), avGfp (SEQ ID NO: 101), vtatp (SEQ ID NO: 102), Gaavp (SEQ ID NO: 103), Gtavp (SEQ ID NO: 104), nsavp (SEQ ID NO: 105), GIGId (SEQ ID NO: 106), andkd (SEQ ID NO: 107), dpvtd (SEQ ID NO: 108), drlph (SEQ ID NO: 109), pwvdw (SEQ ID NO: 110), yylyw (SEQ ID NO:111), Gvww (SEQ ID NO:112), hwGpa (SEQ ID NO: 113), svGpk (SEQ ID NO: 114), srlGI (SEQ ID NO: 115), nylvv (SEQ ID NO: 116), wtkvv (SEQ ID NO: 117), plnvl (SEQ ID NO: 118), llsvf (SEQ ID NO: 119), Gltvf (SEQ ID NO: 120), Glysh (SEQ ID NO: 121), Gnwhw (SEQ ID NO: 122), Gkwvk (SEQ ID NO: 123), Irftf (SEQ ID NO: 124), lrfch (SEQ ID NO: 125), veptv (SEQ ID NO: 126), phpts (SEQ ID NO: 127), hrpwl (SEQ ID NO: 128), vwyGe (SEQ ID NO: 129), affdd (SEQ ID NO: 130), eyeGt (SEQ ID NO:131), andap (SEQ ID NO:132), ytnhp (SEQ ID NO: 133), tsGkn (SEQ ID NO: 134), tnehs (SEQ ID NO:135), skehs (SEQ ID NO: 136), nvsth (SEQ ID NO:137), ntrvk (SEQ ID NO: 138), Gttst (SEQ ID NO: 139), Ghnpn (SEQ ID NO: 140), tkGnl (SEQ ID NO: 141), lplrs (SEQ ID NO: 142), wlsdk (SEQ ID NO: 143), nlfda (SEQ ID NO: 144), kdlvw (SEQ ID NO: 145), akpkf (SEQ ID NO: 146), dpafa (SEQ ID NO: 147), skevd (SEQ ID NO: 148), edlvk (SEQ ID NO: 149), aakrG (SEQ ID NO:150), tsthG (SEQ ID NO: 151), senfd (SEQ ID NO: 152), eprnn (SEQ ID NO: 153), avtr (SEQ ID NO:154), dynGp (SEQ ID NO: 155), dyGvd (SEQ ID NO: 156), skdfd (SEQ ID NO: 157), fdtta (SEQ ID NO: 158), ykdld (SEQ ID NO: 159), nkvyG (SEQ ID NO: 160), kdkdw (SEQ ID NO:161), nekew (SEQ ID NO: 162), srkew (SEQ ID NO: 163), ywkde (SEQ ID NO: 164), lykkd (SEQ ID NO: 165), vwhkd (SEQ ID NO: 166), dkwdk (SEQ ID NO: 167), hyndk (SEQ ID NO: 168), hwnkd (SEQ ID NO: 169), kywkd (SEQ ID NO:170), hfwkd (SEQ ID NO: 171), kynkd (SEQ ID NO: 172), eneth (SEQ ID NO: 174), ddeks (SEQ ID NO: 175), efekd (SEQ ID NO: 176), sGnkd (SEQ ID NO: 177), ekkav (SEQ ID NO: 178), ekflt (SEQ ID NO:179), thrdt (SEQ ID NO: 180), ealpp (SEQ ID NO: 181), raavG (SEQ ID NO: 182), hvads (SEQ ID NO: 183), hleGt (SEQ ID NO: 184), kdpfs (SEQ ID NO: 185), rptwk (SEQ ID NO:186), avstv (SEQ ID NO: 187), yGnfw (SEQ ID NO:188), wnllG (SEQ ID NO: 189), wahGk (SEQ ID NO: 190), spGhG (SEQ ID NO: 191), wvGkp (SEQ ID NO: 192), yeeew (SEQ ID NO: 193), aayy (SEQ ID NO:194), aalwdsattl (SEQ ID NO: 195), flttt (SEQ ID NO: 196), dlfrd (SEQ ID NO: 197), eprrn (SEQ ID NO: 198), tkded (SEQ ID NO: 199), pvwkd (SEQ ID NO:200), wGthw (SEQ ID NO:201), yahnw (SEQ ID NO:202), Gekyh (SEQ ID NO:203), hekwy (SEQ ID NO:204), lvryt (SEQ ID NO: 205), hkdyp (SEQ ID NO:206), kpfGp (SEQ ID NO:207), rwwna (SEQ ID NO:208), trtp (SEQ ID NO:209), kkwGs (SEQ ID NO:210), hhGld (SEQ ID NO:211), vyeGt (SEQ ID NO:212), aGfpv (SEQ ID NO:213), ppwkd (SEQ ID NO:214), or rrkhf (SEQ ID NO:215).

2. The EPI of claim 1 , wherein the synthetic peptide ligand is cyclic.

3. The EPI of claim 1 , wherein the synthetic peptide ligand comprises a 1,4-substituted-1,2,3-triazole residue (Tz4) or a 1,5-substituted-1,2,3-triazole residue (Tz5).

4. The EPI of claim 3 , wherein the synthetic peptide ligand comprises a 1,4-substituted-1,2,3-triazole residue (Tz4).

5. The EPI of claim 3 , wherein the synthetic peptide ligand comprises a 1,5-substituted-1,2,3-triazole residue (Tz5).

6. The EPI of claim 1 , wherein the synthetic peptide ligand was identified by non-catalyzed in situ click chemistry screening of a combinatorial peptide library.

7. The EPI of claim 1 , wherein the SARS-CoV-2 protein is a SARS-CoV-2 spike protein.

8. The EPI of claim 7 , wherein the epitope has the amino acid sequence YGFQPTNGVGYQ (SEQ ID NO:72), CNGVEGENCYGPLQS (SEQ ID NO:73), SPDVDLGDISGINA (SEQ ID NO:74), SCVIRGDEVRQCAPG (SEQ ID NO:75), YGVSPTKLNDLCFTNV (SEQ ID NO:76), TNLCPFGEVENAT (SEQ ID NO:77), TESNKKFLPFQQFGRDIA (SEQ ID NO:78), or GQTGKIADYNYKL (SEQ ID NO:79).

9. The EPI of claim 1 , wherein the antibody-recruiting moiety comprises an epitope recognized by an antibody that mediates recognition and phagocytosis of the target by an immune cell.

10. The EPI of claim 9 , wherein the epitope recognized by an antibody that mediates recognition and phagocytosis of the target by an immune cell is an immunogen endogenously recognized by a mammalian immune system.

11. The EPI of claim 9 , wherein the epitope recognized by an antibody that mediates recognition and phagocytosis of the target by an immune cell is an immunogen endogenously recognized by a human immune system.

12. The EPI of claim 9 , wherein the epitope recognized by an antibody that mediates recognition and phagocytosis of the target by an immune cell is 2,4-dinitrophenyl (DNP), alpha-galactose, galactose(alpha1-3)galactose, beta-lactam, 1,3-diketone, avidin, fluorescein, fluorescein-DNP, or nitrophenol.

13. The EPI of claim 1 , wherein the synthetic peptide ligand is comprised in a multi-ligand, wherein the multi-ligand further comprises a second ligand covalently linked to the synthetic peptide ligand, wherein the second ligand has affinity for a second epitope on the SARS-CoV-2 protein exposed on a surface of the target, and wherein the multi-ligand can simultaneously bind to the epitope and to the second epitope on the SARS-CoV-2 protein.

14. A pharmaceutical composition comprising the EPI of claim 1 and a pharmaceutically acceptable carrier.

15. A method of stimulating an immune reaction to a SARS-COV-2 virus in a subject, the method comprising administering the pharmaceutical composition of claim 14 to the subject, wherein the SARS-CoV-2 virus in the subject is the taregt of the EPI.

Assignees

• Inst Systems Biology
• Us Army

Inventors

• Heath James R
• Idso Matthew
• Winton Alexander J
• Coppock Matthew B
• Liu sanchao

Classifications

• A61K38/08

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K38/07

  Tetrapeptides · CPC title

• C07K5/1008

  the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala · CPC title

• C07K5/1013

  the side chain containing O or S as heteroatoms, e.g. Cys, Ser · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title