Chimeric VlsE Protein for Lyme Borreliosis Diagnosis
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Solution Overview
Problem
Current serological assays for diagnosing Lyme borreliosis face challenges due to insufficient specificity and sensitivity, particularly due to cross-reactivities with other pathogens and genetic diversity of Borrelia burgdorferi, leading to variable performance in detecting pathogenic antibodies.
Innovation Solution
A Borrelia chimeric protein is developed, comprising sequences from the extracellular domain of the VlsE protein and an IR6 region from different Borrelia species, which forms immunological complexes with antibodies, enhancing diagnostic specificity and sensitivity by incorporating sequences with high identity and flexibility, such as SEQ ID NOs: 1, 6, 7, and 8, and optionally VR6 from SEQ ID NO: 9, for use in kits and methods for in vitro diagnosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional serological assays using ultrasound-treated cell samples of Borrelia burgdorferi sensu lato are used, then the diagnosis can be performed, but the specificity is insufficient due to cross-reactivities with other pathogens
Solution Approach 1:
The patent divides the diagnostic antigen into specific protein components (VlsE, DbpA, OspC) from different Borrelia species. By segmenting the antigen into discrete, well-defined proteins rather than using whole cell samples, the assay targets specific Borrelia antigens that reduce cross-reactivity with other pathogens while maintaining sensitivity for detecting Lyme borreliosis antibodies.
Solution Approach 2:
The patent applies local quality by selecting specific proteins (VlsE, DbpA, OspC) that have distinct antigenic properties for different Borrelia species. Each protein region is chosen to capture species-specific epitopes, allowing the assay to differentiate between B. burgdorferi sensu stricto, B. garinii, and B. afzelii, thereby improving diagnostic specificity.
2Reliability
If conventional serological assays are used, then the diagnosis can be performed, but the sensitivity is variable due to genetic diversity of Borrelia burgdorferi
Solution Approach 1:
The patent employs a multi-functional antigen panel comprising VlsE, DbpA, and OspC proteins from multiple Borrelia species. This universal approach ensures that at least one antigen will bind to antibodies produced against any given Borrelia species, thereby maintaining high diagnostic sensitivity across the genetic diversity of pathogenic Borrelia.
Solution Approach 2:
The patent creates a composite antigen system by combining multiple different Borrelia proteins (VlsE, DbpA, OspC) from different species into a single diagnostic assay. This composite approach captures the antigenic diversity of Borrelia burgdorferi sensu lato, ensuring broad detection capability across genetically diverse strains.
3Reliability
If ultrasound-treated cell samples are used as antigens, then the assay can be performed, but the performance levels in terms of specificity and sensitivity are highly variable
Solution Approach 1:
The patent extracts specific recombinant proteins (VlsE, DbpA, OspC) from Borrelia cells and uses these purified proteins as antigens instead of whole cell samples. This extraction of defined protein components eliminates the variability inherent in ultrasound-treated cell samples while maintaining diagnostic performance, and the recombinant production simplifies antigen preparation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The chimeric protein significantly improves the detection of IgGs and IgMs in Lyme borreliosis, achieving high sensitivity and specificity across various stages of the infection, including early stages where symptoms may be asymptomatic, and reduces false negatives and false positives in serological tests.
Implementation Method 1
the chimeric protein comprising (or consisting essentially of or else consisting of) sequences from the extracellular domain of a VlsE protein of a first Borrelia species and sequences from an IR6 region of a VlsE protein of a second Borrelia species... capable of forming an immunological complex with antibodies produced following a Borrelia infection
Data Source
AI summary
A nucleic acid encoding a chimeric protein, the chimeric protein including (i) at least one amino acid sequence having at least 50% sequence identity with any of the amino acid sequences selected from the group consisting of SEQ ID NOS: 1-5, and (ii) at least one amino acid sequence having at least 80% sequence identity with any of the amino acid sequences selected from the group consisting of SEQ ID NOS: 6-8. The chimeric protein includes at least one amino acid sequence of (i) and at least one amino acid sequence of (ii) that are from different Borrelia strains or species.