Peptides and assays for the diagnosis of lyme disease
AssigneeThe Administrators of the Tulane Educational Fund
InventorsMario T. Philipp, Fang Ting Liang
Life of this patent
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Abstract
A peptide consisting of an invariable 26-amino-acid-long region, named IR6, which is antigenically conversed among strains and species of the B. burgdorferi sensu lato complex, and immunodominant in both human and nonhuman primate hosts is described. This peptide is characterized by the sequence MKKDDQIAAAMVLRGMAKDGQFALKD (SEQ ID NO:1). This peptide is useful for rapid and specific diagnosis of Lyme disease, as are proteins containing this peptide and nucleic acid sequences encoding this peptide and these proteins.
Claims28
An isolated, recombinant or synthetic peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, wherein said peptide binds in a mammalian biological sample antibodies specific to the causative agent of Lyme borreliosis.
An isolated, recombinant or synthetic peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, said peptide consisting of SEQ ID NO:
- 1.
A modified peptide of the immunodominant invariable region 6 of the VlsE protein of SEQ ID NO:
- 1, wherein one or more amino acids selected from the group consisting of D4, M11, V12, Q21, and L24 of SEQ ID NO:
- 1 are substituted with a conservative amino acid replacement.
An isolated, recombinant or synthetic peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, said peptide consisting of amino acid residues 241-266 of SEQ ID NO:
- 11.
An isolated, recombinant or synthetic peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, said peptide consisting of amino acid residues 150-175 of SEQ ID NO:
- 10.
An isolated, recombinant or synthetic peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, wherein said peptide binds in a mammalian biological sample antibodies specific to the causative agent of Lyme borreliosis, wherein said sequence is coupled or fused to a second moiety via an optional terminal amino acid linker or chemical coupling agent.
A peptide selected from the group consisting of:
- (a). a peptide consisting of SEQ ID NO:
- 1
- (b). the peptide of (a), wherein an amino acid is added to the amino or carboxyl terminus thereof, and
- (c). the peptide of (a), wherein an amino acid is deleted from the amino or carboxyl terminus thereof,
- wherein each peptide (a) through (c) binds in a mammalian biological sample antibodies specific to the causative agent of Lyme disease.
A peptide selected from the group consisting of:
- (a). a peptide consisting of amino acid residues 241-266 of SEQ ID NO:
- 11, wherein an amino acid is deleted from the amino or carboxyl terminus thereof, and
- (b). a peptide consisting of amino acid residues 241-266 of SEQ ID NO:
- 11, wherein an amino acid is added to the amino or carboxyl terminus thereof,
- wherein each peptide (a) through (b) binds in a mammalian biological sample antibodies specific to the causative agent of Lyme disease.
A peptide selected from the group consisting of:
- (a). a peptide consisting of amino acid residues 150-175 of SEQ ID NO:
- 12, wherein an amino acid is deleted from the amino or carboxyl terminus thereof, and
- (b). a peptide consisting of amino acid residues 150-175 of SEQ ID NO:
- 12, wherein an amino acid is added to the amino or carboxyl terminus thereof,
- wherein each peptide (a) through (b) binds in a mammalian biological sample antibodies specific to the causative agent of Lyme disease.
A diagnostic reagent comprising a peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borelliosis, which peptide binds to antibodies specific to the causative agent of Lyme borreliosis, in a mammalian biological sample, and a second moiety selected from the group consisting of a detectable level and a substrate for immobilizing said peptide.
A composition comprising a peptide, wherein said peptide binds in a mammalian biological sample to antibodies specific to the causative agent of Lyme borreliosis, said peptide selected from the group consisting of:
- (a). a peptide consisting of SEQ ID NO:
- 1,
- (b). the peptide of (a), wherein one or more amino acids selected from the group consisting of D4, M11, V12, Q21, and L24 of SEQ ID NO:
- 1 are replaced with a conservative residue amino acid substitution,
- (c). a peptide consisting of amino acid residues 241-266 of SEQ ID NO:
- 11,
- (d). a peptide consisting of amino acid residues 150-175 of SEQ ID NO:
- 10, and
- (e). the peptides of (a) through (d), wherein an amino acid deleted is deleted from the carboxyl terminus thereof,
- (f). the peptides of (a) through (d), wherein an amino acid is added to the carboxyl terminus thereof,
- wherein each peptide (a) through (f) binds in a mammalian biological sample antibodies specific to the causative agent of Lyme disease.
A composition comprising a peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, wherein said peptide binds in a mammalian biological sample antibodies specific to the causative agent of Lyme borreliosis, a second borrelia antigen selected from the group consisting of OspA, OspB, OspC, BmpA, BmpB, BmpC, and BmpD of B. burgdorferi, and a pharmaceutically acceptable carrier.
A kit for diagnosing Lyme borreliosis in a human or animal comprising a peptide consisting of the immunodominant invariable region 6 of the VlsE protein isolated from a borrelia species that causes Lyme borreliosis, wherein said peptide binds in a mammalian biological sample antibodies specific to the causative agent of Lyme borreliosis, and at least one component selected from the group consisting of a detectable label which produces a detectable signal and a substrate which immobilizes said peptide.
A kit for diagnosing Lyme borreliosis in a human or animal comprising a peptide, wherein said peptide binds in a mammalian biological sample antibodies specific to the causative agent of Lyme borreliosis and is selected from the group consisting of:
- (a). a peptide consisting of SEQ ID NO:
- 1,
- (b). a modified peptide of (a), wherein one or more amino acids selected from the group consisting of D4, M11, V12, Q21, and L24 of SEQ ID NO:
- 1 are substituted with a conservative amino acid replacement,
- (c). a peptide consisting of amino acid residues 241-266 of SEQ ID NO:
- 11,
- (d). a peptide consisting of amino acid residues 150-175 of SEQ ID NO:
- 10,
- (e). a peptide of (a) through (d) wherein an amino acid is deleted from the amino or carboxyl terminus thereof,
- (f). a peptide of (a) through (d) wherein an amino acid is added to the amino or carboxyl terminus thereof,
- wherein each peptide (a) through (f) binds in a mammalian biological sample antibodies specific to the causative agent of Lyme disease, and
- at least one other additional component selected from the group consisting of a detectable label and a substrate which immobilizes said peptide.
A kit for diagnosing Lyme borreliosis in a human or animal comprising the peptide consisting of SEQ ID NO:
- 1 and at least one component selected from the group consisting of a detectable label and a substrate which immobilizes said peptide.
Dependencies are inferred from the claim text.