Claims
- 1. A peptide comprising an amino acid sequence substantially homologous to the amino acid sequence of a fragment of a pyrogenic exotoxin, and derivatives of said peptide, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins.
- 2. A peptide comprising an amino acid sequence substantially homologous to the amino acid sequence of a fragment of a pyrogenic exotoxin, and derivatives of said peptide capable of antagonizing toxin-mediated activation of T cells.
- 3. A peptide comprising an amino acid sequence substantially homologous to the amino acid sequence of a fragment of a pyrogenic exotoxin, and derivatives of said peptide, capable of protecting against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins.
- 4. A peptide according to claim 1 or claim 2 or claim 3, wherein said pyrogenic exotoxin is a bacterial exotoxin.
- 5. A peptide according to claim 4 wherein said exotoxin is produced by Staphylococcus aureus or Streptococcus pyogenes.
- 6. A peptide according to claim 5 comprising an amino acid sequence substantially homologous to the amino acid sequence of a fragment of Staphylococcal aureus enterotoxin B (SEB).
- 7. A peptide according to claim 6 comprising the amino acid sequence shown in SEQ ID NO:1 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 8. A peptide according to claim 7 having the amino acid sequence shown in SEQ ID NO:1 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 9. A peptide according to claim 6 comprising the amino acid sequence shown in SEQ ID NO:2 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 10. A peptide according to claim 9 having the amino acid sequence shown in SEQ ID NO:2 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 11. A peptide according to claim 6 comprising the amino acid sequence shown in SEQ ID NO:3 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 12. A peptide according to claim 11 having the amino acid sequence shown in SEQ ID NO:3 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 13. A peptide according to claim 6 comprising the amino acid sequence shown in SEQ ID NO:4 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 14. A peptide according to claim 13 having the amino acid sequence shown in SEQ ID NO:4 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by at least one pyrogenic exotoxin and/or of antagonizing toxin-mediated activation of T cells.
- 15. A peptide according to claim 1, wherein said fragment may be further linked through its N-terminus to a lauryl-cysteine (LC) residue and/or through its C-terminus to a cysteine (C) residue, or to other residue/s suitable for linking said peptide to adjuvant/s for immunization.
- 16. A peptide according to claim 15 having the amino acid sequence shown in SEQ ID NO:5 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 17. A peptide according to claim 15 having the amino acid sequence shown in SEQ ID NO:6 and derivatives thereof capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 18. A peptide according to claim 1, in the form of a dimer, a multimer or in a constrained conformation.
- 19. A peptide according to claim 18, having the amino acid sequence shown in SEQ ID NO:7 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 20. A peptide according to claim 18 having the amino acid sequence shown in SEQ ID NO:8 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 21. A peptide according to claim 18 which is conformationally constrained by internal bridges, short-range cyclizations, extension or other chemical modification.
- 22. A peptide according to claim 21 having the amino acid sequence shown in SEQ ID NO:9 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 23. A peptide according to claim 21 extended at the N-terminus and/or C-terminus thereof with amino acid residue/s identical to those in the corresponding position/s of said pyrogenic exotoxin or with different amino acid residue/s, which may be naturally occurring or synthetic amino acid residue/s.
- 24. A peptide according to claim 23 having the amino acid sequence shown in SEQ ID NO:10 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 25. A peptide according to claim 23 comprising the amino acid sequence shown in SEQ ID NO:11 and derivatives thereof, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and/or of antagonizing toxin-mediated activation of T cells.
- 26. A peptide according to claim 1, capable of inhibiting expression of pyrogenic toxin-induced mRNA encoded by the IL-2, IFN-γ or TNF-β genes.
- 27. A peptide according to claim 1, capable of eliciting the production of antibodies that block T-cell activation.
- 28. A pharmaceutical composition for the treatment or prophylaxis of toxin-mediated activation of T cells, comprising as active ingredient a therapeutically effective amount of at least one peptide or derivative thereof according to claim 2.
- 29. A pharmaceutical composition for protecting against toxic shock induced by a pyrogenic exotoxin or a mixture of pyrogenic exotoxins, comprising as active ingredient a therapeutically effective amount of at least one peptide or derivative thereof according to claim 3.
- 30. A vaccine for conferring immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins comprising as active ingredient an immunologically effective amount of at least one peptide or derivative thereof according to claim 1.
- 31. A vaccine according to claim 30 further comprising a suitable immunization adjuvant selected from proteosomes, KLH or alum or combinations thereof.
- 32. A vaccine according to claim 29 wherein said immunizing adjuvant is a combination of proteosomes and alum or is a combination of KLH and alum.
- 33. A vaccine according to claim 32 for enhancing production of antibodies that block T cell activation.
- 34. A method for treating harmful effects and toxic shock induced by at least one pyrogenic exotoxin comprising administering to a patient in need of such treatment a therapeutically effective amount of a composition according to claim 28.
- 35. A method according to claim 34 wherein said harmful effect is food poisoning.
- 36. A method for treating harmful effects and toxic shock induced by at least one pyrogenic exotoxin comprising administering to a patient in need of such treatment a therapeutically effective amount of at least one peptide according to claim 2.
- 37. A method according to claim 36 for treating food poisoning induced by a pyrogenic exotoxin.
- 38. A method for preventing harmful effects, toxic shock and death induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins comprising administering to a patient in need of such treatment a therapeutically effective amount of a composition according to claim 27 or a therapeutically effective amount of at least one peptide according to claim 2 or claim 3.
- 39. A method for conferring immunity to toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins, comprising administering to a patient an effective immunizing amount of a vaccine according to claim 30 or of at least one peptide according to claim 1.
- 40. Use of a peptide according to claim 1 in the preparation of a vaccine according to claim 30, or of a peptide according to claim 2 in the preparation of a pharmaceutical composition according to claim 27.
- 41. Antibodies directed against a peptide according to claim 27 which block T-cell activation.
- 42. An antiserum containing antibodies directed against a peptide according to claim 26, which peptide is capable of eliciting the production of said antibodies, preferably in the presence of a suitable immunization adjuvant.
- 43. An antiserum according to claim 42 wherein said suitable immunizing adjuvant is proteosome, KLH or alum or combinations thereof.
- 44. An antiserum according to claim 43 wherein said immunizing adjuvant is a combination of proteosomes and alum or is a combination of KLH and alum.
- 45. An antiserum according to claim 42 which is a domestic animal antiserum.
- 46. An antiserum according to claim 42 capable of alleviating harmful effects and toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins.
- 47. A method for assessing the efficacy of a vaccine for conferring immunity against one or more pyrogenic toxins comprising determining the ability of serum from an immunized individual to antagonize toxin-mediated activation of T cells.
- 48. A method according to claim 47 wherein the ability of serum from an immunized individual to antagonize toxin-mediated activation of T cells is determined by measuring the inhibition of expression of pyrogenic toxin-induced mRNA encoded by the IL-2, IFN-γ or TNF-0 genes.
- 49. A kit for assessing the efficacy of a vaccine for conferring immunity against one or more pyrogenic toxins comprising determining the ability of serum from an immunized individual to antagonize toxin-mediated activation of T cells by the method of claim 47.
Priority Claims (1)
Number |
Date |
Country |
Kind |
119938 |
Dec 1996 |
IL |
|
Government Interests
[0001] The U.S. Government has a nonexclusive, nontransferable, irrevocable paid-up licensee to practice or have practiced this invention for or on its behalf as provided for by the terms of Contract No. DAMD17-93-C-3108 awarded by the U.S. Department of the Army.
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
PCT/IL97/00438 |
Dec 1997 |
US |
Child |
09150947 |
Sep 1998 |
US |