Chimeric proteins comprising borrelia polypeptides and uses therefor

• US 6,248,562 B1
• Filed: 04/29/1994
• Issued: 06/19/2001
• Est. Priority Date: 11/01/1993
• Status: Expired due to Term

• Current Assignee: Brookhaven Science Associates, LLC (Government of the United States of America), The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: Brookhaven Science Associates, LLC (Government of the United States of America), The Research Foundation for The State University of New York (State University of New York)
• Inventors: Luft, Benjamin J., Dunn, John J.
• Primary Examiner(s): Bui, Phuong T.
• Application Number:
  US08/235,836
• Time in Patent Office: 2,608 Days
• Field of Search: 530/350, 424/263.1, 424/184.1, 424/234.1, 424/185.1, 424/190.1, 424/192.1, 424/203.1, 435/69.1, 435/69.3, 435/69.7, 435/71.1
• US Class Current: 435/69.3
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/20 from Spirochaetales (O), e.g. Treponema, Leptospira
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Chimeric nucleic acids encoding chimeric Borrelia proteins consisting of at least two antigenic polypeptides from corresponding and/or non-corresponding proteins from the same and/or different species of Borrelia, are disclosed. Chimeric proteins encoded by the nucleic acid sequences are also disclosed. The chimeric proteins are useful as vaccine immunogens against Lyme borreliosis, as well as for immunodiagnostic reagents.

Claims

1. A protein having an amino acid sequence selected from the group consisting of:

SEQ ID NO. 86, SEQ ID NO. 89, SEQ ID NO. 92, SEQ ID NO. 95, SEQ ID NO. 98, SEQ ID NO. 101, SEQ ID NO. 104, SEQ ID NO. 107, SEQ ID NO. 110, SEQ ID NO. 112, SEQ ID NO. 114, SEQ ID NO. 116, SEQ ID NO. 118, SEQ ID NO. 120, SEQ ID NO. 122, SEQ ID NO. 138, SEQ ID NO. 140, SEQ ID NO. 142, and SEQ ID NO. 144.

2. A chimeric protein comprising two polypeptides derived from outer surface protein A from different Lyme Disease causing strains of Borrelia wherein the first polypeptide comprises outer surface protein A from the N-terminus to and including a conserved tryptophan and the second polypeptide comprises outer surface protein A from the conserved tryptophan to the C-terminus of the protein wherein said first polypeptide and said second polypeptide are from different strains of Lyme Disease causing Borrelia and wherein the amino acid sequence of said chimeric protein is not the same as the amino acid sequence of either outer surface protein A from which said first polypeptide and said second polypeptide are obtained and wherein each polypeptide retains antigenicity in the chimeric protein.

3. The chimeric protein of claim 2, wherein the polypeptides are derived from two genospecies of Lyme Disease causing Borrelia.

4. A chimeric OspA protein comprising

a) a first polypeptide, comprising outer surface protein A from the N-terminus to and including a conserved tryptophan, wherein said first polypeptide includes hypervariable regions comprising residues 120 through 140, residues 150 through 180, and residues 200 through 217, and

b) a second polypeptide comprising outer surface protein A from the conserved tryptophan to the C-terminus of the protein;

wherein the Lyme disease causing strain of Borrelia from which at least one of the group consisting of;

any one of said hypervariable regions and said second polypeptide differs from the Lyme disease causing strain of Borrelia from which the remainder of said first polypeptide is obtained, and wherein the hypervariable region comprising residues 200 through 217 and said second polypeptide are from different Lyme disease causing strains of Borrelia, and wherein the amino acid sequence of said chimeric OspA protein is not the same as the amino acid sequence of any outer surface protein A from which said first polypeptide and said second polypeptide are obtained and wherein the chimeric protein retains antigenicity representative of the OspA protein of the parent Borrelia strains.

5. The chimeric protein of claim 4, wherein at least two of the polypeptides within the chimeric protein are from different genospecies of Borrelia.