Methods, compositions, and systems for detecting coronavirus neutralizing antibodies
Inventors
Petropoulos, Christos J. • Wrin, Mary T. • DiTirro, Danielle
Assignees
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Publication Number
US-12366581-B2
Publication Date
2025-07-22
Expiration Date
Abstract
The present disclosure relates to methods, compositions, and systems for detecting whether a subject exposed to a coronavirus has developed a neutralizing antibody response. Also disclosed are methods for determining whether a patient infected by a coronavirus is likely to respond to treatment with an antibody preparation. Also disclosed are methods for detecting the level of neutralizing antibody response in a sample of serum from a subject exposed to a coronavirus or to a coronavirus vaccine.
Core Innovation
The invention provides a pseudovirus-based, luciferase reporter assay for detecting and quantifying coronavirus neutralizing antibodies and for assessing likelihood of response to antibody therapeutics. The assay uses coronavirus spike and an indicator nucleic acid to generate viral particles that produce a detectable luciferase signal when the particles enter target cells expressing ACE-2, and optionally TMPRSS2.
In the presence of subject serum or plasma or an antibody preparation, the assay measures reduction of the detectable luciferase signal, where reduced signal indicates neutralization. The approach includes evaluation of spike mutations and variants by comparing viral particles carrying control coronavirus spike protein versus nucleic acid encoding a coronavirus spike protein that comprises a mutation, followed by contacting with antibody-containing samples and measuring the indicator signal to determine changes in susceptibility.
The document describes engineered producer and target cell compositions used in the system, including ACE2/TMPRSS2 target contexts and specific human cell lines. It also reports assay performance details such as specificity, sensitivity, precision, linearity, interference, and stability, and includes example results for SARS-CoV-2 variants including B.1.1.7, B.1.351, B.1.1.28.1, B.1.427/B.1.429, and the D614G mutation and other single mutations.
Claims Coverage
The independent claims cover a genetically modified human target cell composition and a related evaluation approach for measuring antibody neutralization and assessing susceptibility of viral particles to antibodies, with an indicator nucleic acid readout. The inventive features identified below are grounded in the independent claim content and its stated dependent refinements that define the system components and evaluation context.
Genetically modified human kidney target cell expressing ACE-2 and TMPRSS2
A composition comprising a cell that has been genetically modified to be a target cell, wherein the target cell expresses an angiotensin-converting enzyme 2 receptor (ACE-2) and a human airway transmembrane trypsin-like serine protease (TMPRSS2), and wherein the target cell is a human kidney cell.
Target cell as 293, 5A10, or 5G7 cells
A composition comprising the genetically modified human kidney target cell system of the target cell being one of 293, 5A10, or 5G7 cells.
Stable expression of ACE-2 and TMPRSS2
A composition wherein the target cells express ACE-2 and TMPRSS2 stably.
Across the independent claim coverage and its refinements, the core inventive structure is a genetically modified human kidney target cell expressing ACE-2 and TMPRSS2, including specified cell lines and optionally stable expression, forming the defined component used in the assay context described for measuring neutralization with an indicator signal.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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