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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 acid 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 comprise as active ingredient at least one peptide according to the invention, or derivative thereof.
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.
Antibodies directed against a 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.
An antiserum containing antibodies directed against a 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 peptide is capable of eliciting the production of said antibodies, preferably in the presence of a suitable immunization adjuvant.
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.
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.
Dependencies are inferred from the claim text.