US2003099634A1PendingUtilityA1

Compositions and methods for eliciting CTL immunity

53
Priority: Aug 26, 1991Filed: Apr 22, 2002Published: May 29, 2003
Est. expiryAug 26, 2011(expired)· nominal 20-yr term from priority
Inventors:Maria VitielloRobert ChesnutAlessandro SetteEsteban CelisHoward Grey
C07K 14/33A61P 31/12C12N 2740/16122C12N 2770/24222C07K 14/005C12N 2740/16322C07K 14/705C12N 2730/10122C12N 2740/16222C12N 2710/20022A61P 31/18C12N 2760/16122A61P 37/04C12N 2740/16022A61K 39/00
53
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Claims

Abstract

Cytotoxic T lymphocyte responses are effectively induced to an antigen of interest, particularly viral, bacterial, parasitic and tumor antigens. Compositions, including pharmaceutical compositions, of CTL-inducing peptide and an adjuvant or a lipidated peptide which induces a helper T cell (HTL) response stimulate the antigen specific CTL response. Among the viral antigens to which the CTL responses are effectively induced in humans are those of hepatitis B. The CTL response may be optimized by a regimen of two or more booster administrations. Cocktails of two or more CTL inducing peptides are employed to optimize epitope and/or MHC class I restricted coverage.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . An immunogenically effective composition comprising: 
 a first peptide comprising an epitope, wherein the first peptide binds to an HLA class I molecule to form an epitope-HLA complex recognized by a human cytotoxic T cell;    a second peptide comprising an epitope, wherein the second peptide binds to an HLA class II molecule to form an epitope-HLA complex recognized by a human helper T cell;    an adjuvant; and    a physiologically acceptable carrier.    
     
     
         2 . The composition of  claim 1 , wherein the second peptide is covalently linked to the first peptide.  
     
     
         3 . The composition of  claim 1 , wherein the second peptide is not linked to the first peptide.  
     
     
         4 . The composition of  claim 1 , wherein the first peptide is linked to the second peptide by a spacer molecule.  
     
     
         5 . The composition of  claim 1 , wherein the epitope is a viral epitope, a bacterial epitope, a parasitic epitope, or a tumor epitope.  
     
     
         6 . The composition of  claim 1 , wherein the first peptide, the second peptide, or the first peptide and second peptide are each from six to thirty amino acid residues in length.  
     
     
         7 . The composition of  claim 1 , wherein the first peptide, the second peptide, or the first peptide and second peptide comprises a plurality of epitopic units.  
     
     
         8 . The composition of  claim 1 , wherein the first peptide is elected from the group consisting of LLAQFTSAI (SEQ ID NO:31), LLVPFVQWFV (SEQ ID NO:32), WLSLLVPFV (SEQ ID NO:33), FLLAQFTSA (SEQ ID NO:34), FLLSLGIHL (SEQ ID NO: 35), ALMPLYACI (SEQ ID NO:36), ILLLCLIFLL (SEQ ID NO:37), KLHLYSHPI (SEQ ID NO:38), VLLDYQGML (SEQ ID NO:39), LLPIFFCLWV (SEQ ID NO:40), VLQAGFFLL (SEQ ID NO:41), YLHTLWKAGI (SEQ ID NO:42), YLHTLWKAGV (SEQ ID NO:43), PLLPIFFCL (SEQ ID NO:44), ILSTLPETTV (SEQ ID NO:45), LLFNILGGWV (SEQ ID NO: 46), LLALLSCLTV (SEQ ID NO:47), YLVAYQATV (SEQ ID NO:48), FLLLADARV (SEQ ID NO:49), ILAGYGAGV (SEQ ID NO:50), DLMGYIPLV (SEQ ID NO:51), YLLPRRGPRL (SEQ ID NO:52), ALSTGLIHL (SEQ ID NO:53), LLALLSCLTI (SEQ ID NO:54), RLIVFPDLGV (SEQ ID NO:55), RLHGLSAFSL (SEQ ID NO:56), ILGGWVAAQL (SEQ ID NO:57), SMVGNWAKV (SEQ ID NO:58), YLVTRHADV (SEQ ID NO:59), VLAALAAYCL (SEQ ID NO:60), LLMGTLGIV (SEQ ID NO:65), YMLDLQPET (SEQ ID NO:66), FAFRDLCIV (SEQ ID NO:67), TLGIVCPIC (SEQ ID NO:68), TLHEYMLDL (SEQ ID NO:69), GTLGIVCPI (SEQ ID NO:70), MLDLQPETT (SEQ ID NO:71), TIHDIILECV (SEQ ID NO:72), VLAEAMSQV (SEQ ID NO:73), LLWKGEGAVV (SEQ ID NO:74), LLWKGEGAV (SEQ ID NO:75), ILKEPVHGV (SEQ ID NO:76), IVGAETFYV (SEQ ID NO:77), IIGAETFYV (SEQ ID NO:78), LWVTVYYGV (SEQ ID NO:79), LMVTVYYGV (SEQ ID NO:80), KMVELVHFL (SEQ ID NO:81), KMVELVHFLL (SEQ ID NO:82), LVFGIELMEV (SEQ ID NO:83), KVLEYVIKV (SEQ ID NO:84), KVADLVGFLL (SEQ ID NO:85), KVAEFVHFL (SEQ ID NO:86), CILESLFRA (SEQ ID NO:87), FLWGPRALA (SEQ ID NO:88), VMIAMEGGHA (SEQ ID NO:89), LVLGTLEEV (SEQ ID NO:90), ALREEEEGV (SEQ ID NO:91), ALAETSYVKV (SEQ ID NO:92), YVIKVSARV (SEQ ID NO:93), and RALAETSYV (SEQ ID NO:94).  
     
     
         9 . The composition of  claim 1 , wherein the second peptide is selected from the group consisting of QYIKANSKFIGITE (SEQ ID NO:95), KIAKMEKASSVFNVVNS (SEQ ID NO:96), DIEKKIAKMEKASSVFNVVNS (SEQ ID NO:97), ISQAVHAAHAEINE (SEQ ID NO:98), PKYVKQNTLKLAT (SEQ ID NO:99), MDIDPYKEFGATVELLSFLP (SEQ ID NO:100), PHHYALRQAILCWGELMYLA (SEQ ID NO:101), LLWFHISCLTFGRETVIEYL (SEQ ID NO:102), EYLVSFGVWIRTPPA (SEQ ID NO:103), and VSFGVWIRTPPAYRPPNAPI (SEQ ID NO:104).  
     
     
         10 . The composition of  claim 1 , wherein the adjuvant is incomplete Freund's adjuvant, complete Freund's adjuvant, alum, aluminum hydroxide, or a lipid.  
     
     
         11 . The composition of  claim 1 , wherein the adjuvant is a lipid.  
     
     
         12 . The composition of  claim 11 , wherein the lipid is linked to the first peptide.  
     
     
         13 . The composition of  claim 11 , wherein the lipid is linked to the second peptide.  
     
     
         14 . The composition of  claim 11 , wherein the lipid is linked to the first and the second peptide.  
     
     
         15 . A method for stimulating an immune response in a human against an epitope, comprising the steps of: 
 (a) providing a first peptide comprising an epitope, wherein the first peptide binds to an HLA class I molecule to form an epitope-HLA complex recognized by a human cytotoxic T cell;    (b) providing a second peptide comprising an epitope, wherein the second peptide binds to an HLA class II molecule to form an epitope-HLA complex recognized by a human helper T cell;    (c) providing an adjuvant; and    (d) administering the first and second peptides and the adjuvant to the human.    
     
     
         16 . The method of  claim 15 , wherein the second peptide is covalently linked to the first peptide.  
     
     
         17 . The method of  claim 15 , wherein the second peptide is not linked to the first peptide.  
     
     
         18 . The method of  claim 15 , wherein the first peptide is linked to the second peptide by a spacer molecule.  
     
     
         19 . The method of  claim 15 , wherein the administration step comprises administering the first peptide, second peptide and the adjuvant concurrently.  
     
     
         20 . The method of  claim 15 , which further comprises, following step (d), a step (e) administering the first and second peptides to the human, whereby the administration steps (d) and (e) are spaced a sufficient interval apart to optimize development of said immune response to the epitopes.  
     
     
         21 . The method of  claim 20 , wherein the administration step (e) comprises administering the second peptide and the first peptide approximately four weeks after the administration step (d).  
     
     
         22 . The method of  claim 15 , wherein the epitope is a viral epitope, a bacterial epitope, a parasitic epitope, or a tumor epitope.  
     
     
         23 . The method of  claim 15 , wherein the first and second peptides are administered prophylactically.  
     
     
         24 . The method of  claim 15 , wherein the first peptide and/or the second peptide are each from six to thirty amino acid residues in length.  
     
     
         25 . The method of  claim 15 , wherein the first peptide, the second peptide, or the first peptide and second peptide comprises a plurality of epitopic units.  
     
     
         26 . The composition of  claim 15 , wherein the first peptide is selected from the group consisting of LLAQFTSAI (SEQ ID NO:31), LLVPFVQWFV (SEQ ID NO:32), WLSLLVPFV (SEQ ID NO:33), FLLAQFTSA (SEQ ID NO:34), FLLSLGIHL (SEQ ID NO: 35), ALMPLYACI (SEQ ID NO:36), ILLLCLIFLL (SEQ ID NO:37), KLHLYSHPI (SEQ ID NO:38), VLLDYQGML (SEQ ID NO:39), LLPIFFCLWV (SEQ ID NO:40), VLQAGFFLL (SEQ ID NO:41), YLHTLWKAGI (SEQ ID NO:42), YLHTLWKAGV (SEQ ID NO:43), PLLPIFFCL (SEQ ID NO:44), ILSTLPETTV (SEQ ID NO:45), LLFNILGGWV (SEQ ID NO: 46), LLALLSCLTV (SEQ ID NO:47), YLVAYQATV (SEQ ID NO:48), FLLLADARV (SEQ ID NO:49), ILAGYGAGV (SEQ ID NO:50), DLMGYIPLV (SEQ ID NO:51), YLLPRRGPRL (SEQ ID NO:52), ALSTGLIHL (SEQ ID NO:53), LLALLSCLTI (SEQ ID NO:54), RLIVFPDLGV (SEQ ID NO:55), RLHGLSAFSL (SEQ ID NO:56), ILGGWVAAQL (SEQ ID NO:57), SMVGNWAKV (SEQ ID NO:58), YLVTRHADV (SEQ ID NO:59), VLAALAAYCL (SEQ ID NO:60), LLMGTLGIV (SEQ ID NO:65), YMLDLQPET (SEQ ID NO:66), FAFRDLCIV (SEQ ID NO:67), TLGIVCPIC (SEQ ID NO:68), TLHEYMLDL (SEQ ID NO:69), GTLGIVCPI (SEQ ID NO:70), MLDLQPETT (SEQ ID NO:71), TIHDIILECV (SEQ ID NO:72), VLAEAMSQV (SEQ ID NO:73), LLWKGEGAVV (SEQ ID NO:74), LLWKGEGAV (SEQ ID NO:75), ILKEPVHGV (SEQ ID NO:76), IVGAETFYV (SEQ ID NO:77), IIGAETFYV (SEQ ID NO:78), LWVTVYYGV (SEQ ID NO:79), LMVTVYYGV (SEQ ID NO:80), KMVELVHFL (SEQ ID NO:81), KMVELVHFLL (SEQ ID NO:82), LVFGIELMEV (SEQ ID NO:83), KVLEYVIKV (SEQ ID NO:84), KVADLVGFLL (SEQ ID NO:85), KVAEFVHFL (SEQ ID NO:86), CILESLFRA (SEQ ID NO:87), FLWGPRALA (SEQ ID NO:88), VMIAMEGGHA (SEQ ID NO:89), LVLGTLEEV (SEQ ID NO:90), ALREEEEGV (SEQ ID NO:91), ALAETSYVKV (SEQ ID NO:92), YVIKVSARV (SEQ ID NO:93), and RALAETSYV (SEQ ID NO:94).  
     
     
         27 . The composition of  claim 15 , wherein the second peptide is selected from the group consisting of QYIKANSKFIGITE (SEQ ID NO:95), KIAKMEKASSVFNVVNS (SEQ ID NO:96), DIEKKIAKMEKASSVFNVVNS (SEQ ID NO:97), ISQAVHAAHAEINE (SEQ ID NO:98), PKYVKQNTLKLAT (SEQ ID NO:99), MDIDPYKEFGATVELLSFLP (SEQ ID NO:100), PHHYALRQAILCWGELMYLA (SEQ ID NO:101), LLWFHISCLTFGRETVIEYL (SEQ ID NO:102), EYLVSFGVWIRTPPA (SEQ ID NO:103), and VSFGVWIRTPPAYRPPNAPI (SEQ ID NO:104).  
     
     
         28 . The method of  claim 15 , wherein the first and the second peptides are administered with a physiologically-acceptable carrier.  
     
     
         29 . The method of  claim 15 , wherein the adjuvant is alum, aluminum hydroxide, or a lipid.  
     
     
         30 . The method of  claim 15 , wherein the first peptide is administered with the lipid.  
     
     
         31 . The method of  claim 30 , wherein the adjuvant is a lipid and the first peptide is linked to the lipid.  
     
     
         32 . The method of  claim 15 , wherein the second peptide is administered with the adjuvant.  
     
     
         33 . The method of  claim 32 , wherein the second peptide is linked to the adjuvant.  
     
     
         34 . The method of  claim 15 , wherein the first peptide and the second peptide are administered with an adjuvant.  
     
     
         35 . The method of  claim 34 , wherein the first peptide and the second peptide are both linked to the adjuvant.

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