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AssigneeYissum Research Development Company of the Hebrew University of Jerusalem
InventorsRaymond Kaempfer, Gila Arad
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The invention relates to peptides comprising an amino acid sequence homologous to the amino sequence of a fragment of a pyrogenic exotoxin, and functional derivatives of said peptides, capable of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins. Preferred peptides comprise an amino acid sequence homologous to the amino sequence of a fragment of Staphylococcal aureus enterotoxin B (SEB). The invention also relates to broad spectrum pharmaceutical compositions for the treatment, protection against or short term prophylaxis of toxin-mediated activation of T cells, comprising as active ingredient at least one peptide according to the invention or derivative thereof, and to broad spectrum vaccines for conferring long term immunity against toxic shock induced by at least one pyrogenic exotoxin are provided. The vaccines comprising as active ingredient at least one peptide according to the invention, or derivative thereof.
An isolated and purified peptide having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin, which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, and any functional fragments or derivatives of said peptide, wherein said isolated peptide does not have toxin agonist activity and is capable of antagonizing toxin-mediated activation of T lymphocytes and/or of eliciting protective immunity against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins and protecting against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins.
An isolated and purified peptide having the amino acid sequence selected from the group consisting of any one of SEQ ID NO:1 to SEQ ID NO:11 and SEQ ID NO:13 to SEQ ID NO:15.
An isolated and purified peptide having the amino acid sequence according to SEQ ID NO:2.
An isolated and purified peptide having the amino acid sequence according to SEQ ID NO:13.
An isolated and purified peptide having an amino acid sequence Xaa(n)KXaa(8)D, wherein Xaa is an amino acid and n is zero or an integer of from 1 to 10, and wherein said peptide does not have toxin agonist activity.
An isolated and purified peptide having an amino acid sequence Xaa(n)KXaa(3)TXaaQEXaaD, wherein Xaa is an amino acid and n is zero or an integer of from 1 to 10, and wherein said peptide does not have toxin agonist activity.
An isolated and purified peptide having an amino acid sequence Xaa(n)KKXaa(6)LD, wherein Xaa is an amino acid and n is zero or an integer of from 1 to 10, and wherein said peptide does not have toxin agonist activity.
An isolated an purified peptide having an amino acid sequence Ch.aa-Xaa(2)-Hb.aa-X-Hb.aa-Po.aa-Po.aa-Hb.aa-D, wherein Xaa is an amino acid, n is zero or an integer of from 1 to 10, Ch.aa is a charged amino acid, Hb.aa is a hydrophobic amino acid and Po.aa is a polar amino acid and wherein said peptide does not have toxin agonist activity.
A composition which inhibits pyrogenic exotoxin-mediated activation of T-lymphocytes and protects against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins, comprising as an active ingredient an isolated and purified peptide, in an amount effective to inhibit exotoxin-induced expression of an RNA encoded by the IL-2, INF-γ and/or TNF-β genes, wherein said peptide is having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, wherein said peptide does not have toxin agonist activity, which composition optionally further comprises pharmaceutically acceptable carrier, diluent, adjuvant and/or excipient.
An immunogenic composition for eliciting antibodies that block pyrogenic exotoxin mediated activation of T-lymphocytes comprising as an active ingredient in an amount effective to elicit said antibodies, an isolated and purified peptide having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin, which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, wherein said peptide does not have toxin agonist activity, which composition optionally further comprises pharmaceutically acceptable carrier, diluent, adjuvant and/or excipient.
A pharmaceutical composition for the treatment of incapacitation induced by at least one pyrogenic exotoxin comprising an isolated and purified peptide having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin, which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, wherein said peptide does not have toxin agonist activity, which composition optionally further comprises pharmaceutically acceptable carrier, diluent, adjuvant and/or excipient.
A method of inhibiting pyrogenic exotoxin-mediated activation of T-lymphocytes and protecting against toxic shock induced by a pyrogenic exotoxin or by a mixture of pyrogenic exotoxins, in a patient in need of such treatment comprising administering to said patient an inhibitory effective amount of an isolated and purified peptide or of a composition comprising the same, which peptide having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, wherein said peptide does not have toxin agonist activity.
A method of eliciting protective immunity against a toxic shock induced by a pyrogenic exotoxin in a patient in need of such treatment comprising administering to said patient an isolated and purified peptide or of an immunogenic composition comprising the same, which peptide having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, wherein said peptide does not have toxin agonist activity.
A method of preventing and/or treating incapacitation induced by at least one pyrogenic exotoxin comprising administering to a patient in need of such treatment at least one therapeutically effective dose of an isolated and purified peptide or of a composition comprising the same, which peptide having an amino acid sequence homologous to an amino acid sequence of a domain of a pyrogenic exotoxin which domain forms a central turn in the exotoxin starting within β-strand 7 and connecting the β-strand 7, via short β-strand 8, to α-helix 4, and ending within α-helix 4, based on the domain numbering of SEB, wherein said peptide does not have toxin agonist activity.
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.
Dependencies are inferred from the claim text.