Epitope Focusing via Variable Antigen Concentration
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Solution Overview
Problem
Current vaccine approaches have been ineffective against pathogens like HIV-1 and influenza virus due to their ability to undergo antigenic drift, leading to evasion of neutralization by antibodies.
Innovation Solution
An immunogenic composition comprising at least 6 antigens, each with a common target epitope, is developed. The antigens are designed such that each antigen has an individual concentration insufficient to be immunogenic alone, but collectively they elicit an immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional subunit vaccine strategies are used targeting immunodominant epitopes, then early neutralizing antibodies are generated, but the pathogen undergoes antigenic drift and evades neutralization
Solution Approach 1:
The vaccine composition is segmented into multiple antigen variants (at least 6), each containing the same conserved target epitope but with different variable regions. This segmentation allows the vaccine to present multiple versions of the target epitope simultaneously, preventing the pathogen from evading through single-point mutations while maintaining focused immune response to the conserved region
Solution Approach 2:
The patent applies local quality by creating antigens with heterogeneous variable regions while maintaining a homogeneous conserved target epitope. The variable regions are designed to be sufficiently different to prevent antigenic drift evasion, while the conserved epitope region maintains identical or highly similar sequences to focus the immune response on a specific vulnerable site that is essential for pathogen function
2Reliability
If multiple antigen variants are used to prevent antigenic drift evasion, then vaccine reliability improves, but the complexity of vaccine composition increases
Solution Approach 1:
All antigen variants in the composition serve the dual function of (1) presenting the conserved target epitope to focus immune response and (2) providing variable regions to prevent antigenic drift evasion. This multi-functionality reduces overall complexity compared to designs requiring separate components for each function
Solution Approach 2:
The patent systematically varies specific parameters (amino acid sequences in variable regions) while holding other parameters (conserved epitope sequence, overall protein fold, expression levels) constant. This controlled parameter change approach allows optimization of immune response focus while managing compositional complexity through defined variation rules
3Duration of action of stationary object
If the vaccine targets conserved epitopes rather than immunodominant epitopes, then antibody longevity improves, but the initial immune response strength decreases
Solution Approach 1:
The vaccine composition is designed in advance to present multiple antigen variants with identical conserved epitopes, pre-positioning the immune system to recognize and respond to the conserved region from the first exposure. This preliminary action ensures that B cells specific for the conserved epitope are activated immediately, overcoming the typical weakness of conserved epitope targeting
Solution Approach 2:
The patent merges multiple antigen variants into a single vaccine composition, combining the advantages of both immunodominant epitopes (strong immune activation) and conserved epitopes (long-lasting protection). The synergistic effect of multiple variants focusing on the same conserved target amplifies the initial immune response while maintaining antibody longevity
Data Source
AI summary
The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.