Peptides for vaccine

Abstract

The present invention relates to compositions comprising peptides for preventing or treating allergy to house dust mites, and in particular to optimal combinations of peptides for preventing or treating said allergy.

1 . A composition comprising:
 (i) (a) at least one of the polypeptides Tim07B (KIPAGELQIIDKIDA), Tim 10B (KYTVFETALKKAITAMSE), Tim 04A (WGAIWRIDTPDKL), Tim 07G (FKVAATAANAAPANDK) or a variant of any thereof;
 (b) at least one of the polypeptides Ber01 (SGKAFGAMAKKGQED), Ber02 (FIPMKSSWGA), Ber02C (KSSWGAIWRIDPKKPLK), Ber 02B KDSDEFIPMKSSWGAIWR or a variant of any thereof; and 
 (c) at least one of the polypeptides Bio04A (LKKAVTAMSEAEK), Rye09B (PEVKYAVFEAALTKAIT), Bio02A (KYDAYVATLTEALR), Bio03A (KFIPTLVAAVKQAYAAKQ), Rye 08A (ETYKFIPSLEAAVKQAY), Rye 05C(NAGFKAAVAAAANAPPK), or a variant of any thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a), (b) or (c); or 
 
   (ii) at least four different polypeptides selected from:
 (a) Tim07B (KIPAGELQIIDKIDA) or a variant thereof; 
 (b) Ber01 (SGKAFGAMAKKGQED) or a variant thereof; 
 (c) Bio04A (LKKAVTAMSEAEK) or a variant thereof; 
 (d) Rye09B (PEVKYAVFEAALTKAIT) or a variant thereof; 
 (e) Ber02 (FIPMKSSWGA) or a variant thereof; 
 (f) Ber02C (KSSWGAIWRIDPKKPLK) or a variant thereof; 
 (g) Bio03A (KFIPTLVAAVKQAYAAKQ) or a variant thereof; and 
 (h) Bio02A (KYDAYVATLTEALR) or a variant thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a) to (h). 
 
   
     
     
         2 . A composition according to  claim 1 , comprising:
 a) the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof,   b) the polypeptide Ber01 (SGKAFGAMAKKGQED) or a said variant thereof, and   c) the polypeptide Bio04A (LKKAVTAMSEAEK) or a said variant thereof.   
     
     
         3 . A composition according to  claim 1 , comprising:
 (a) the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof;   (b) at least one of the polypeptides of Ber01 (SGKAFGAMAKKGQED), Ber02 (FIPMKSSWGA), and Ber02C (KSSWGAIWRIDPKKPLK) or a said variant of any thereof; and   (c) at least one of the polypeptides of Bio04A (LKKAVTAMSEAEK), Rye09B (PEVKYAVFEAALTKAIT), Bio02A (KYDAYVATLTEALR), and Bio03A (KFIPTLVAAVKQAYAAKQ) or a said variant of any thereof; and   (d) at least one additional polypeptide of (b) or (c) not selected above.   
     
     
         4 . A composition according to  claim 3 , comprising the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof, the polypeptide Ber01 (SGKAFGAMAKKGQED) or a said variant thereof, the polypeptide Bio04A (LKKAVTAMSEAEK) or a said variant thereof, and at least one additional polypeptide of  claim 4  (b) or (c) not selected above. 
     
     
         5 . The composition according to  claim 1 , comprising at least one said variant which is 9 to 20 or 13 to 17 amino acids in length. 
     
     
         6 . The composition according to  claim 1 , wherein one or more of the said polypeptides or variants thereof have one or more modifications selected from the following:
 (i) N terminal acetylation;   (ii) C terminal amidation;   (iii) one or more hydrogens on the side chain amines of Arginine and/or Lysine replaced with a methylene group;   (iv) glycosylation; and   (v) phosphorylation.   
     
     
         7 . The composition according to  claim 1 , which is a solution wherein each said polypeptide or variant thereof has a concentration in the range of 0.03 to 200 nmol/ml, 0.3 to 200 nmol/ml, 5 to 200 nmol/ml or 30 to 120 nmol/ml. 
     
     
         8 . A composition according to  claim 1 , which is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier or diluent. 
     
     
         9 . The composition according to  claim 8 , which is formulated for oral administration, topical administration, nasal administration, subcutaneous administration, sublingual administration, intradermal administration, buccal administration, epidermal or patch administration or for administration by inhalation or by injection. 
     
     
         10 . An in vitro method of determining whether T cells from an individual recognize a composition as defined in  claim 1 , which method comprises the steps of contacting said T cells with said composition, detecting whether said T cells are stimulated by said composition and determining thereby whether said individual has, or is at risk of having, an allergy to grass pollen. 
     
     
         11 . A composition according to  claim 1 , comprising a said variant which has 1, 2, 3 or 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (i) (a), (b) or (c) or (ii) (a) to (h); and/or has 1, 2, 3, 4 or 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (i) (a), (b) or (c) or (ii) (a) to (h). 
     
     
         12 . A kit for use in preventing or treating allergy to grass pollen, comprising instructions for use and:
 (i) (a) at least one of the polypeptides Tim07B (KIPAGELQIIDKIDA), Tim 10B (KYTVFETALKKAITAMSE), Tim 04A (WGAIWRIDTPDKL), Tim 07G (FKVAATAANAAPANDK) or a variant of any thereof;
 (b) at least one of the polypeptides Ber01 (SGKAFGAMAKKGQED), Ber02 (FIPMKSSWGA), Ber02C (KSSWGAIWRIDPKKPLK), Ber 02B KDSDEFIPMKSSWGAIWR or a variant of any thereof; and 
 (c) at least one of the polypeptides Bio04A (LKKAVTAMSEAEK), Rye09B (PEVKYAVFEAALTKAIT), Bio02A (KYDAYVATLTEALR), Bio03A (KFIPTLVAAVKQAYAAKQ), Rye 08A (ETYKFIPSLEAAVKQAY), Rye 05C(NAGFKAAVAAAANAPPK), or a variant of any thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a), (b) or (c); or 
 
   (ii) at least four different polypeptides selected from:
 (a) Tim07B (KIPAGELQIIDKIDA) or a variant thereof; 
 (b) Ber01 (SGKAFGAMAKKGQED) or a variant thereof; 
 (c) Bio04A (LKKAVTAMSEAEK) or a variant thereof; 
 (d) Rye09B (PEVKYAVFEAALTKAIT) or a variant thereof; 
 (e) Ber02 (FIPMKSSWGA) or a variant thereof; 
 (f) Ber02C (KSSWGAIWRIDPKKPLK) or a variant thereof; 
 (g) Bio03A (KFIPTLVAAVKQAYAAKQ) or a variant thereof; and 
 (h) Bio02A (KYDAYVATLTEALR) or a variant thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a) to (h). 
 
   
     
     
         13 . A kit according to  claim 12 , comprising:
 a) the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof,   b) the polypeptide Ber01 (SGKAFGAMAKKGQED) or a said variant thereof, and   c) the polypeptide Bio04A (LKKAVTAMSEAEK) or a said variant thereof.   
     
     
         14 . A process for preparing a pharmaceutical formulation for use in preventing or treating allergy to grass pollen, which process comprises the step of formulating:
 (i) (a) at least one of the polypeptides Tim07B (KIPAGELQIIDKIDA), Tim 10B (KYTVFETALKKAITAMSE), Tim 04A (WGAIWRIDTPDKL), Tim 07G (FKVAATAANAAPANDK) or a variant of any thereof;
 (b) at least one of the polypeptides Ber01 (SGKAFGAMAKKGQED), Ber02 (FIPMKSSWGA), Ber02C (KSSWGAIWRIDPKKPLK), Ber 02B KDSDEFIPMKSSWGAIWR or a variant of any thereof; and 
 (c) at least one of the polypeptides Bio04A (LKKAVTAMSEAEK), Rye09B (PEVKYAVFEAALTKAIT), Bio02A (KYDAYVATLTEALR), Bio03A (KFIPTLVAAVKQAYAAKQ), Rye 08A (ETYKFIPSLEAAVKQAY), Rye 05C(NAGFKAAVAAAANAPPK), or a variant of any thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a), (b) or (c); or 
 
   (ii) at least four different polypeptides selected from:
 (a) Tim07B (KIPAGELQIIDKIDA) or a variant thereof; 
 (b) Ber01 (SGKAFGAMAKKGQED) or a variant thereof; 
 (c) Bio04A (LKKAVTAMSEAEK) or a variant thereof; 
 (d) Rye09B (PEVKYAVFEAALTKAIT) or a variant thereof; 
 (e) Ber02 (FIPMKSSWGA) or a variant thereof; 
 (f) Ber02C (KSSWGAIWRIDPKKPLK) or a variant thereof; 
 (g) Bio03A (KFIPTLVAAVKQAYAAKQ) or a variant thereof; and 
 (h) Bio02A (KYDAYVATLTEALR) or a variant thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a) to (h); together with a pharmaceutically acceptable carrier or diluent. 
 
   
     
     
         15 . A process according to  claim 14 , wherein the pharmaceutical formulation comprises:
 a) the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof,   b) the polypeptide Ber01 (SGKAFGAMAKKGQED) or a said variant thereof, and   c) the polypeptide Bio04A (LKKAVTAMSEAEK) or a said variant thereof.   
     
     
         16 . A method of preventing or treating allergy to grass pollen, the method comprising administering to a subject in need of such treatment a therapeutically effective amount of:
 (i) (a) at least one of the polypeptides Tim07B (KIPAGELQIIDKIDA), Tim 10B (KYTVFETALKKAITAMSE), Tim 04A (WGAIWRIDTPDKL), Tim 07G (FKVAATAANAAPANDK) or a variant of any thereof;
 (b) at least one of the polypeptides Ber01 (SGKAFGAMAKKGQED), Ber02 (FIPMKSSWGA), Ber02C (KSSWGAIWRIDPKKPLK), Ber 02B KDSDEFIPMKSSWGAIWR or a variant of any thereof; and 
 (c) at least one of the polypeptides Bio04A (LKKAVTAMSEAEK), Rye09B (PEVKYAVFEAALTKAIT), Bio02A (KYDAYVATLTEALR), Bio03A (KFIPTLVAAVKQAYAAKQ), Rye 08A (ETYKFIPSLEAAVKQAY), Rye 05C(NAGFKAAVAAAANAPPK), or a variant of any thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a), (b) or (c); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a), (b) or (c); or 
 
   (ii) at least four different polypeptides selected from:
 (a) Tim07B (KIPAGELQIIDKIDA) or a variant thereof; 
 (b) Ber01 (SGKAFGAMAKKGQED) or a variant thereof; 
 (c) Bio04A (LKKAVTAMSEAEK) or a variant thereof; 
 (d) Rye09B (PEVKYAVFEAALTKAIT) or a variant thereof; 
 (e) Ber02 (FIPMKSSWGA) or a variant thereof; 
 (f) Ber02C (KSSWGAIWRIDPKKPLK) or a variant thereof; 
 (g) Bio03A (KFIPTLVAAVKQAYAAKQ) or a variant thereof; and 
 (h) Bio02A (KYDAYVATLTEALR) or a variant thereof; 
 wherein said variant:
 I) is a longer polypeptide of up to 30 amino acids in length which comprises the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 II) has 1 to 4 amino acid deletions from the N-terminal and/or C-terminal end of the sequence of the corresponding polypeptide specified in (a) to (h); and/or 
 III) has 1 to 5 conservative amino acid substitutions in the sequence of the corresponding polypeptide specified in (a) to (h); 
 
   
     
     
         17 . A method according to  claim 16 , wherein the method comprises administering to a subject in need of such treatment a therapeutically effective amount of:
 a) the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof,   b) the polypeptide Ber01 (SGKAFGAMAKKGQED) or a said variant thereof, and   c) the polypeptide Bio04A (LKKAVTAMSEAEK) or a said variant thereof.   
     
     
         18 . A method according to  claim 16 , wherein the method comprises administering to a subject in need of such treatment a therapeutically effective amount of:
 (a) the polypeptide Tim07B (KIPAGELQIIDKIDA) or a said variant thereof;   (b) at least one of the polypeptides of Ber01 (SGKAFGAMAKKGQED), Ber02 (FIPMKSSWGA), and Ber02C (KSSWGAIWRIDPKKPLK) or a said variant of any thereof; and   (c) at least one of the polypeptides Bio04A (LKKAVTAMSEAEK), Rye09B (PEVKYAVFEAALTKAIT), Bio02A (KYDAYVATLTEALR), Bio03A (KFIPTLVAAVKQAYAAKQ) or a said variant of any thereof; and   (d) at least one additional polypeptide of (b) or (c) not selected above.   
     
     
         19 . A method according to  claim 16 , wherein the said polypeptides or variants thereof are administered orally, topically, parenterally, subcutaneously, by inhalation, intravenously, intramuscularly, intrasternally, transdermally, intradermally, sublingually, intranasally, buccally, by infusion techniques or by suppository. 
     
     
         20 . A method according to  claim 16 , wherein the said polypeptides or variants thereof are provided as an injectable solution, suspension or emulsion and administered via parenteral, subcutaneous, epidermal, intradermal, intramuscular, intraarterial, intraperitoneal, intravenous injection using a conventional needle and syringe, or using a liquid jet injection system.