Chimeric Leptospira Protein for Early Serological Diagnosis

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current diagnostic methods for leptospirosis, such as the Microagglutination Test (MAT), have low sensitivity in the early stages of the disease, leading to delayed antibiotic therapy and high mortality rates.

Innovation Solution

A chimeric protein composed of 10 immunogenic conserved proteins from L. interrogans, specifically LIC10123, LIC13059, LIC13050, LIC12615, LIC11636, LIC11352, LIC11122, LIC11089, LIC10713, and LIC13434, is developed to detect IgM and IgG antibodies in serum samples, enhancing early diagnosis through ELISA and biosensor platforms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the Microagglutination Test (MAT) is used for leptospirosis diagnosis, then the test can detect antibodies in patient serum, but the sensitivity is low in early stages of the disease

Engineering Contradiction:
Improvediagnosis sensitivityVSAvoiddiagnosis delay
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies composite materials by creating a chimeric protein that combines epitopic regions from multiple different leptospiral proteins (including LipL32, OmpL1, and other outer membrane proteins) into a single diagnostic antigen. This composite antigen structure allows the test to detect a broader range of antibodies produced during early infection, thereby increasing diagnosis sensitivity and enabling earlier detection compared to traditional single-antigen MAT tests

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If the Microagglutination Test (MAT) is used for leptospirosis diagnosis, then the test can identify agglutination of leptospires, but the test is difficult to perform

Engineering Contradiction:
Improvediagnosis accuracyVSAvoidtest complexity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts the essential diagnostic function from the complex MAT procedure by isolating and utilizing specific epitopic regions of leptospiral proteins as soluble antigens. This extraction allows the diagnostic capability to be transferred to simpler formats such as ELISA or rapid immunochromatographic tests, maintaining diagnostic accuracy while eliminating the technical complexity of manipulating live leptospires and observing agglutination

Inventive Principle:
Principle #2Taking out (Extraction)

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 increases sensitivity for leptospirosis diagnosis, detecting IgM and IgG antibodies in 75% of false-negative MAT samples, facilitating rapid and accurate early detection.

Implementation Method 1

The chimeric protein composed of 10 immunogenic conserved proteins from L. interrogans... detects IgM and IgG antibodies in serum samples

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP4678654A1Chimeric protein, host microbial cell, process for obtaining said chimeric protein, leptospirosis serological diagnostic kit, in vitro method for early serological diagnosis of leptospirosis and use of said chimeric protein
Publication Date: 2026.01.14 INSTITUTO BUTANTAN
  • EP4678654A1 patent drawingFigure 1
  • EP4678654A1 patent drawingFigure 2
  • EP4678654A1 patent drawing

AI summary

The present invention relates to a chimeric protein composed of specific regions of proteins proven to be conserved and present on the surface of L. interrogans selected from the group consisting of LIC10123, LIC13059, LIC13050, LIC12615, LIC11636, LIC11352, LIC11122, LIC11089, LIC10713, and LIC13434, wherein the specific regions consist of the amino acid sequences as established by SEQ ID NO: 2, 4, 6, 7, 9, 11, 13, 14, 16, 18, 20, and 22. The present invention further relates to a host microbial cell comprising the chimeric gene consisting of the nucleotide sequence as established by SEQ ID NO: 25, the chimeric gene and an expression cassette. In addition, the present invention relates to a process for obtaining said chimeric protein and a leptospirosis serological diagnostic kit comprising the chimeric protein of the present invention. Additionally, the present invention relates to an in vitro method for early serological diagnosis of leptospirosis and the use of said chimeric protein for early serological diagnosis of leptospirosis by detecting IgM and/or IgG antibodies in serum samples from patients suspected of having leptospirosis.