Biosensor Immune Response Characterization for Dengue Vaccine
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Solution Overview
Problem
Current assays lack accuracy in determining the binding affinity or avidity of antibodies specific for viruses, particularly those directed to particulate antigens preserving conformational and quaternary epitopes, and fail to effectively characterize the immune response to dengue virus compositions and vaccines.
Innovation Solution
A method involving virus-like particles (VLPs) or live/inactivated viruses attached to biosensors using surface plasmon resonance or biolayer interferometry to measure the affinity, binding kinetics, and concentration of antibodies, combined with serum sample analysis and multiple assay techniques to assess immune response parameters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional assays are used to measure antibody binding, then the measurement process is simple, but the measurement precision and accuracy are insufficient for particulate antigens with conformational and quaternary epitopes
Solution Approach 1:
The patent employs biosensors as intermediary devices that directly interact with particulate antigens (viruses or VLPs) to measure antibody binding. The biosensor surface is functionalized to present antigens in a native-like configuration, allowing accurate measurement of binding affinity while maintaining assay feasibility through automated reading systems.
Solution Approach 2:
The patent replaces conventional mechanical/chemical assay systems (such as ELISA or plate-based methods) with biosensor-based optical detection systems. This substitution enables real-time, label-free measurement of antibody-antigen interactions with higher precision, particularly for particulate antigens where conformational integrity is critical.
2Ease of operation
If neutralization assays are used to measure antibody response, then the assay is easy to perform, but the measurement does not capture all antibody effector functions and correlates poorly with vaccine efficacy
Solution Approach 1:
The patent develops a multi-parameter characterization system that simultaneously measures multiple aspects of antibody response including binding affinity, neutralization capacity, and other effector functions. This universal approach provides a more comprehensive and reliable prediction of vaccine efficacy compared to single-assay methods.
Solution Approach 2:
The patent measures multiple immune response parameters (binding affinity, neutralization titer, avidity indices) rather than relying on a single parameter. By changing from a single-parameter to multi-parameter measurement approach, the system achieves better correlation with vaccine efficacy while maintaining operational feasibility through integrated assay platforms.
3Ease of manufacture
If affinity maturation is measured using traditional methods, then the process is straightforward, but the degree of affinity maturation driven by vaccination cannot be accurately measured
Solution Approach 1:
The patent uses biosensors as intermediary measurement tools that enable precise detection of antibody affinity changes. The biosensor system provides a controlled interaction environment that accurately reflects in vivo binding conditions, allowing reliable measurement of affinity maturation driven by vaccination while maintaining procedural simplicity.
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
This approach provides accurate and real-time analysis of antibody interactions, enabling the characterization of immune responses and prediction of vaccine efficacy by determining key immune response parameters such as neutralizing antibodies and avidity indices.
Implementation Method 1
surface plasmon resonance or biolayer interferometry to measure the affinity, binding kinetics
Implementation Method 2
surface plasmon resonance or biolayer interferometry to measure the affinity, binding kinetics
Data Source
AI summary
The present invention relates to a method for characterizing the immune response of a subject to a tetravalent dengue virus composition by performing the method for determining affinity, binding kinetics and/or concentration of an antibody or of an antibody mixture and at least one other method. In a further embodiment, the present invention relates to a method for characterizing the immune response of a subject to a virus-containing vaccine composition by performing a combination of assays. In a further embodiment, the present invention relates to a method for predicting protective efficacy of a dengue vaccine candidate. In another embodiment the present invention relates to a method for preparing a vaccine formulation.