Method for down-regulating IL5 activity
View Patent ↗Improvements in therapy and prevention of conditions characterized by an elevated level of eosinophil leukocytes, i.e. conditions such as asthma and other chronic allergic diseases are disclosed. A method is provided for down-regulating interleukin 5 (IL5) by enabling the production of antibodies against IL5 thereby reducing the level of activity of eosinophils.
1. A method of in vivo down-regulation of interleukin 5 (IL5) activity in an animal, including a human being, the method comprising administering an immunogenically effective amount of
at least one T H epitope-containing IL5 polypeptide wherein said T H epitope-containing IL5 polypeptide differs from the animal's autologous IL5 polypeptide in that the T H epitope-containing IL5 polypeptide comprises at least one foreign T H epitope introduced into the amino acid sequence of the animal's autologous IL5 polypeptide, whereby immunization of the animal with the T H epitope-containing IL5 polypeptide produces antibodies against the animal's autologous IL5 polypeptide and whereby said T H epitope-containing IL5 polypeptide reacts to the same extent with an atiserum raised against the animal's autologous IL5 as does the autologous IL5 and wherein the T H epitope-containing IL5 polypeptide comprises a foreign T H epitope in at least one of loops 1-3 or in the amino acid residues C-terminal to helix D, said loops and said helix D corresponding to those shown in FIG. 3 for human and murine IL5, SEQ ID NO: 1, SEQ ID NO: 12, respectively.
2. The method according to claim 1 , wherein the foreign T H epitope is immunodominant in the animal.
3. The method according to claim 1 , wherein the foreign T H epitope is promiscuous.
4. The method according to claim 3 , wherein the at least one foreign T H epitope is selected from a natural promiscuous T-cell epitope and an artificial MHC-II binding peptide sequence.
5. The method according to claim 4 , wherein the natural T H epitope is selected from the group consisting of a Tetanus toxoid epitope, a diphtheria toxoid epitope, an influenza virus hemagluttinin epitope, and a P. faciparum CS epitope.
6. The method according to claim 5 , wherein said Tetanus toxoid epitope is P2 or P30.
7. The method according to claim 1 , wherein the IL5 polypeptide is a human IL5 polypeptide.
8. The method according to claim 7 , wherein the human IL5 polypeptide has been modified by substituting at least one amino acid sequence in SEQ ID NO: 1 with at least one amino acid sequence of equal or different length thereby giving rise to a foreign T H epitope, wherein substitute amino acid residues are selected from the group consisting of residues 87-90, residues 88-91, residues 32-43, residues 33-43, residues 59-64, residues 86-91, and residues 110-113.
9. The method according to claim 1 , wherein the T H epitope-containing IL5 polypeptide is administered together with an adjuvant which facilitates breaking of autotolerance to autoantigens.
10. The method according to claim 9 , wherein the adjuvant is selected from the group consisting of an immune targeting adjuvant; an immune modulating adjuvant; an oil formulation; a polymer; a micelle forming adjuvant; a saponin; an immunostimulating complex matrix (as ISCOM matrix); DDA; aluminum adjuvants; DNA adjuvants; γ-inulin; and an encapsulating adjuvant.
11. The method according to claim 1 , wherein an effective amount of the T H epitope-containing IL5 polypeptide is administered to the animal via a route selected from the parenteral route; the peritoneal route; the oral route; the buccal route; the sublingual route; the epidural route; the spinal route; the anal route; and the intracranial route.
12. The method according to claim 11 , wherein said potential route is a member selected from the group consisting of the intradermal, the subdermal, the intracutaneous, the subcutaneous, and the intramuscular routes.
13. The method according to claim 11 , wherein the effective amount is between 0.5 μg and 2,000 μg of the IL5 polypeptide.
14. The method according to claim 11 , which includes at least one administration of the IL5 polypeptide per year.
15. The method according to claim 11 , wherein the IL5 polypeptide is contained in a virtual lymph node (VLN) device.
16. The method according to claim 10 , wherein said immune modulating adjuvant is a member selected from the group consisting of a toxin, a cytokine and a mycobacterial derivative.
17. A method for treating asthma or other chronic allergic conditions characterized by eosinophilia, the method comprising administering to a patient in need thereof an immunogenically effective amount of
at least one T H epitope-containing IL5 polypeptide wherein said T H epitope-containing IL5 polypeptide differs from the animal's autologous IL5 polypeptide in that the T H epitope-containing IL5 polypeptide comprises at least one foreign T H epitope inserted into the amino acid sequence of the animal's autologous IL5 polypeptide, whereby immunization of the animal with the T H epitope-containing IL5 polypeptide produces antibodies against the animal's autologous IL5 polypeptide whereby said T H epitope-containing IL5 polypeptide reacts to the same extent with an antiserum raised against the animal's autologous IL5 as does the autologous IL5 and wherein the T H epitope-containing IL5 polypeptide comprises a foreign T H epitope in at least one of loops 1-3 or in the amino acid residues C-terminal to helix-D, said loops and said helix D corresponding to those shown in FIG. 3 for human and murine IL5, SEQ ID NO: 1 and SEQ ID NO: 12, respectively.