Recombinant Immune Complex Antigen Insertion for Dengue Serotype Balance

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Solution Overview

Problem

Existing vaccines struggle to generate balanced immune responses against multiple serotypes of pathogens like dengue virus, particularly due to antibody-dependent enhancement, necessitating the development of a vaccine platform that can effectively target multiple serotypes.

Innovation Solution

A multivalent recombinant immune complex (RIC) platform is developed, comprising immunoglobulin heavy chains with epitope tags and fragments of antigens from multiple viral serotypes, allowing for the formation of self-multimerizing immune complexes that enhance immunogenicity and binding to complement receptors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a single-antigen vaccine is used, then the vaccine structure is simple and easy to manufacture, but it cannot generate balanced immune responses against multiple serotypes

Engineering Contradiction:

Improveability to target multiple serotypesVSAvoidvaccine structure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent creates a universal RIC platform where a single antibody scaffold with epitope tag can bind multiple different antigens from various serotypes. The antibody-antigen-antibody structure allows one RIC construct to simultaneously target multiple serotypes through the multivalent antigen component, achieving multi-functionality without requiring separate vaccines for each serotype

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent merges multiple antigens from different serotypes into a single RIC construct by fusing them to the C-terminus of the immunoglobulin heavy chain. This combining approach integrates multiple protective antigens (e.g., DENV1-4 domain III) into one unified vaccine molecule that elicits balanced immune responses against all included serotypes

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If antibody-dependent enhancement is present, then natural immune response occurs, but it worsens the immune response against multiple serotypes

Engineering Contradiction:

Improveimmune response balanceVSAvoidantibody-dependent enhancement

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful antibody-dependent enhancement phenomenon into a beneficial effect by deliberately incorporating the epitope tag that normally causes ADE into the vaccine structure. The epitope tag serves dual purposes: it enables RIC formation through antibody binding while simultaneously serving as the antigen that elicits protective neutralizing antibodies, thereby converting the harmful cross-reactivity into protective immunity

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The epitope tag acts as an intermediary element that mediates between the antibody scaffold and the antigen. It provides a standardized binding interface for RIC formation while presenting the antigenic determinants that stimulate protective immune responses, thereby controlling and directing the immune response rather than allowing uncontrolled ADE

Inventive Principle:

Principle #24Intermediary (Mediator)

3Quantity of substance

If multiple antigens are incorporated into RIC, then immunogenicity is enhanced, but the manufacturing process becomes more complex

Engineering Contradiction:

Improvenumber of antigens per RICVSAvoidproduction process simplicity

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent segments the vaccine design into modular components: a standardized antibody scaffold with epitope tag and C-terminal antigen fusions. This segmentation allows different antigen combinations to be assembled using the same basic platform, simplifying manufacturing by reusing the proven antibody-RIC formation protocol across multiple antigen variants rather than developing entirely new constructs for each serotype combination

Inventive Principle:

Principle #1Segmentation

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 RIC platform effectively generates immune responses against multiple dengue virus serotypes, enhancing immunogenicity and receptor binding, thereby improving vaccine efficacy.

Implementation Method 1

an immunoglobulin heavy chain; at least one epitope tag, wherein the immunoglobulin heavy chain binds the epitope tag

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS20250228925A1Methods and related aspects for increasing antigenic insertion sites on a recombinant immune complex platform

Publication Date: 2025.07.17 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA

AI summary

Provided herein is a multivalent recombinant immune complex (RIC) that includes an immunoglobulin heavy chain; at least one epitope tag, wherein the immunoglobulin heavy chain binds the epitope tag; and at least fragments of antigens from at two viral serotypes. In some embodiments, the antigens comprise a dengue virus (DENV) domain III antigen. Related methods and other aspects are also provided.