Human Neutralizing Antibodies for Japanese Encephalitis Genotype Coverage

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current vaccines against Japanese Encephalitis Virus (JEV) are primarily derived from a single genotype (GIII), which may not be effective against the shifting prevalence of genotype GI, leading to a need for broadly neutralizing antibody responses that can inhibit multiple JEV genotypes.

Innovation Solution

Development of human neutralizing monoclonal antibodies with clone-paired heavy and light chain CDR sequences, which can bind to JEV epitope E-DIII, and their use in detecting and treating JEV infections by administering them to subjects via various routes, including intraperitoneal injection or genetic delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If vaccines are derived from a single genotype (GIII), then vaccine production is simplified and standardized, but the vaccine becomes ineffective against shifting genotype prevalence (GI)

Engineering Contradiction:

Improvevaccine productionVSAvoidgenotype coverage

Core Design Contradiction:

Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent develops human neutralizing monoclonal antibodies that recognize and bind to conserved epitopes on the JEV envelope protein that are present across multiple genotypes (GI, GII, GIII, GIV). This universal recognition capability allows a single antibody or antibody combination to provide protection against diverse JEV strains, resolving the contradiction between manufacturing simplicity and genotype adaptability.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent identifies and targets specific conserved regions on the JEV envelope protein (particularly in domain III) that remain relatively unchanged across different genotypes. By focusing antibody development on these parameter-conserved epitopes rather than variable regions, the invention achieves broad genotype coverage while maintaining standardized production approaches.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If monoclonal antibodies are developed to bind to conserved epitopes, then broad neutralization activity against multiple genotypes is achieved, but antibody development complexity increases

Engineering Contradiction:

Improvegenotype coverageVSAvoidantibody development

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs a systematic preliminary approach to antibody development: first identifying conserved epitope regions through sequence analysis across multiple JEV genotypes, then using these identified targets to guide monoclonal antibody selection and optimization. This preliminary mapping of conserved regions simplifies the subsequent antibody development process by providing clear targets, reducing the search space, and enabling focused development efforts.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If human neutralizing monoclonal antibodies are administered for treatment, then protection against JEV infection is provided, but treatment cost and complexity increase

Engineering Contradiction:

Improveprotection efficacyVSAvoidtreatment administration

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent describes formulating monoclonal antibodies with adjuvants or in combination with other therapeutic agents to enhance their protective efficacy. These formulations act as intermediaries that amplify the antibody's neutralizing activity, allowing lower doses to achieve the same protective effect, thereby reducing treatment complexity and cost while maintaining high reliability.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 antibodies demonstrate neutralization activity against multiple JEV strains, providing protection and reducing the likelihood of infection, and can be used for diagnostic purposes by detecting antigen binding, thus addressing the genotype shift and improving vaccine efficacy.

Implementation Method 1

detecting Japanese Encephalitis virus in said sample by binding of said antibody or antibody fragment to a Japanese Encephalitis virus antigen in said sample

Methodology Applied

Scientific EffectAntigen-antibody binding: