Compositions and methods for screening for Lyme disease

Inventors

Burbelo, Peter D. • Marques, Adriana • Iadarola, Michael J.

Assignees

US Department of Health and Human Services

Abstract

The invention provides compositions, methods, and kits for the diagnosis or detection of infection by a pathogen that causes Lyme disease in a subject.

Core Innovation

The invention provides compositions, methods, and kits for the diagnosis or detection of infection by a pathogen that causes Lyme disease in a subject. It specifically uses isolated peptides or mixtures of peptides, such as those comprising amino acid sequences with high identity to SEQ ID NOS: 1, 2, or 3, derived from Borrelia species pathogens including Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana. The compositions include single peptides or covalently linked peptide mixtures derived from antigenic fragments of VlsE and OspC antigens to detect antibodies in samples from infected subjects.

The problem being solved arises from the difficulty in culturing Borrelia bacteria and the limitations of current testing methods for Lyme disease diagnosis. Clinical diagnosis often relies on exam findings like erythema migrans (EM), but not all patients develop EM or express clear symptoms. Existing serological tests, such as ELISA and Western blot, may lack sensitivity or specificity, especially in early infection stages or in monitoring therapeutic responses due to limited dynamic range and cumbersome procedures. The invention addresses the need for sensitive, specific, and high-throughput assay methods for detecting antibodies to Borrelia sp. infections.

The invention employs the Luciferase Immunoprecipitation System (LIPS) utilizing fusion proteins incorporating antigenic Borrelia peptides linked to a luciferase reporter, which provides quantitative antibody titers with high sensitivity and specificity. The novel synthetic VOVO antigen, consisting of alternating copies of immunoreactive peptides from VlsE and OspC antigens, demonstrated improved sensitivity and specificity over existing tests (such as C6 ELISA) while enabling detection without serum dilution and allowing quantitation over a wide dynamic range. The methods include assays for diagnosing infection, monitoring therapeutic treatment response, and selecting treatment regimens based on antibody binding to the antigenic peptides.

Claims Coverage

This patent includes multiple independent claims focusing on compositions of isolated peptides, nucleic acids encoding these peptides, and related kits. There are three main inventive features articulated in the independent claims.

Overall, the claims cover compositions of isolated peptides derived from Borrelia antigens (particularly SEQ ID NO: 1), nucleic acids encoding these peptides, and kits containing these peptides or nucleic acids, targeting the detection of Lyme disease infection.

Stated Advantages

Documented Applications