Vaccine comprising Amb a 1 peptides for use in the treatment of ragweed allergy
The present invention relates to compositions for preventing or treating allergy to ragweed by tolerization. The compositions are based on combinations of peptide fragments derived from the major allergen in ragweed pollen, Amb a 1. The invention also relates to products, vectors and formulations which may be used to provide polypeptides of the invention in combination. The invention further relates to in vitro methods for determining whether T cells recognize a polypeptide of the invention, and for determining whether an individual has or is at risk of a condition characterized by allergic symptoms in response to a ragweed allergen.
1. A composition suitable for use in treating allergy to ragweed comprising:
(a) at least one polypeptide selected from the group consisting of RDLLENGAIFLPSG (SEQ ID NO: 9), DVFENGAIFVPSG (SEQ ID NO: 8), and KDLLENGAIFVTSG (SEQ ID NO: 7);
(b) at least one polypeptide selected from the group consisting of GMIKSNDGPPI (SEQ ID NO: 1), GLIKSHDGPPV (SEQ ID NO: 2) and GLIKSNDGPAA (SEQ ID NO: 3); and
(c) at least one polypeptide selected from the group consisting of KAGMIPAEPGEA (SEQ ID NO: 10) and SAGMIPAEPGEA (SEQ ID NO: 11),
and an effective amount of a preservative or adjuvant.
2. The composition according to claim 1 , which comprises the polypeptide GMIKSNDGPPI (SEQ ID NO:1); the polypeptide RDLLENGAIFLPSG (SEQ ID NO:9); and the polypeptide SAGMIPAEPGEA (SEQ ID NO:11).
3. The composition according to claim 1 , which further comprises at least one polypeptide selected from a polypeptide of GSSQIWIDHSSLSKS (SEQ ID NO: 4), ETRRSLKTSGAYN (SEQ ID NO: 26), VVNSDKTIDGRGVKVE (SEQ ID NO: 14), AINNDKTIDGRGAKVE (SEQ ID NO: 15), FGFFQVVNNNYD (SEQ ID NO: 27), HGFFQVVNNNYD (SEQ ID NO: 28), KEGTLRFAAAQNRP (SEQ ID NO: 12), or KEGTLRFGAAQNRP (SEQ ID NO: 13); and optionally further comprising a polypeptide of GEAAIKLTSSAGVLS (SEQ ID NO: 16), KGEAAIKLTSSAGVLSK (SEQ ID NO: 19), or KGEAAIKLTSSAGVLSKK (SEQ ID NO: 20).
4. The composition according to claim 1 , which further comprises GMIKSNDGPPI (SEQ ID NO:1); RDLLENGAIFLPSG (SEQ ID NO:9); SAGMIPAEPGEA (SEQ ID NO:11); GSSQIWIDHSSLSKS (SEQ ID NO:4); KEGTLRFAAAQNRP (SEQ ID NO:12); AINNDKTIDGRGAKVE (SEQ ID NO:15); and KGEAAIKLTSSAGVLSKK (SEQ ID NO:20).
5. The composition according to claim 1 , wherein: one or more of the polypeptides have one or more modifications selected from the group consisting of:
(a) N terminal acetylation;
(b) C terminal amidation;
(c) one or more hydrogen on the side chain amines of Arginine and/or Lysine replaced with a methylene group;
(d) glycosylation; and
(e) phosphorylation.
6. The composition according to claim 1 , which is a solution in which each polypeptide has a concentration in the range of 0.03 to 200 nmol/ml.
7. The composition according to claim 1 , which is a solution in which each polypeptide has a concentration in the range of 0.3 to 200 nmol/ml.
8. The composition according to claim 1 , which is a solution in which each polypeptide has a concentration in the range of 30 to 200 nmol/ml.
9. The composition according to claim 1 , which is a pharmaceutical formulation comprising a pharmaceutically acceptable carrier or diluent.
10. The pharmaceutical formulation according to claim 9 , formulated for oral administration, nasal administration, epicutaneous administration, subcutaneous administration, sublingual administration, intradermal administration, buccal administration or for administration by inhalation or by injection.
11. A composition suitable for use in treating allergy to ragweed comprising:
(a) at least one polypeptide selected from the group consisting of RDLLENGAIFLPSG (SEQ ID NO: 9), DVFENGAIFVPSG (SEQ ID NO: 8), and KDLLENGAIFVTSG (SEQ ID NO: 7);
(b) at least one polypeptide selected from the group consisting of GMIKSNDGPPI (SEQ ID NO: 1), GLIKSHDGPPV (SEQ ID NO: 2) and GLIKSNDGPAA (SEQ ID NO: 3); and
(c) at least one polypeptide selected from the group consisting of KAGMIPAEPGEA (SEQ ID NO: 10) and SAGMIPAEPGEA (SEQ ID NO: 11), and
an effective amount of a preservative or adjuvant, wherein each polypeptide is present in an amount of 100 ng to 2 mg.