Mutant fragments of ospa and methods and uses relating thereto
AssigneeValneva Austria GmbH
InventorsUrban Lundberg, Wolfgang Schüler
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Abstract
The present invention relates to compositions and methods for the prevention and treatment of Borrelia infection. Particularly, the present invention relates to a polypeptide comprising a hybrid C-terminal fragment of an outer surface protein A (OspA), a nucleic acid coding the same, an antibody specifically binding the same, a pharmaceutical composition (particularly for use as a medicament or in a method of treating or preventing a Borrelia infection) comprising the polypeptide and/or the nucleic acid and/or the antibody, a method of treating or preventing a Borrelia infection and a method of immunizing a subject.
Claims49
A polypeptide comprising a hybrid C-terminal OspA (outer surface protein A of Borrelia) fragment, wherein the hybrid C-terminal OspA fragment consists, from the N- to C-terminal direction, of
- i) a first OspA portion consisting of amino acids 125-176 or amino acids 126-175 of OspA from a Borrelia strain that is not the corresponding fragment of B. garinii, strain PBr, with SEQ ID NO:
- 8, and
- ii) a second OspA portion consisting of amino acids 176-274 or most preferably amino acids 177-274 of OspA from B. garinii, strain PBr (SEQ ID NO:
- 8), wherein the second OspA fragment is mutant and cystine-stabilized in that it differs from the corresponding wild-type sequence at least by the substitution of the wild-type amino acid at position 182 of SEQ ID NO:
- 8 by a cysteine and by the substitution of the wild-type amino acid at position 269 of SEQ ID NO:
- 8 by a cysteine and wherein a disulfide bond between the cysteine at position 182 and the cysteine at position 269 of said second OspA fragment is present;
- and
- wherein the numbering of the amino acids and of the cysteine substitutions is according to the numbering of corresponding amino acids of the full length OspA of B. burgdorferi s.s., strain B31 (SEQ ID NO:
- 5).
A polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO:
- 1.
A polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO:
- 51.
A polypeptide comprising or consisting of an amino acid sequence of SEQ ID NO:
- 27 (heterodimer of Lip-S4D1-S3hybD1).
A pharmaceutical composition comprising Lip-S1D1-S2D1 (SEQ ID NO:
- 29), Lip-S4D1-S3hybD1 (SEQ ID NO:
- 27) and Lip-S5D1-S6D1 (SEQ ID NO:
- 33).
Dependencies are inferred from the claim text.