Immunogenic Composition for Subdominant Antigen Detection
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Solution Overview
Problem
Conventional vaccine strategies are inadequate for developing effective vaccines against complex and highly biohazardous human pathogens, as they fail to detect responses to subdominant antigens and are limited by technological bottlenecks in studying T cell responses against numerous pathogen proteins.
Innovation Solution
The development of an immunogenic composition using nucleic acid fragments or minigenes derived from a library, which are delivered via a delivery medium to antigen presenting cells, allowing for the simultaneous expression and presentation of multiple antigens and enabling the identification and selection of immunogenic antigens for multi-antigen vaccine compositions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccine strategies use hyperimmunization with whole organisms (e.g., sporozoites), then responses against sporozoite-expressed antigens are boosted, but responses against antigens newly expressed in hepatocytes and subdominant antigens are lost or undetectable
Solution Approach 1:
The patent segments the immune response detection process by using separate assays for different antigen classes. Instead of relying on a single hyperimmunization screen that biases toward sporozoite antigens, the invention employs multiple specialized assays (e.g., ELISPOT, flow cytometry) that can independently detect responses to liver-stage antigens and subdominant antigens, thereby resolving the detection bias problem.
Solution Approach 2:
The patent inverts the conventional approach by starting with naive or partially immunized animals and proactively inducing responses to specific antigen classes before final vaccination. This allows subdominant and liver-stage antigens to be detected early when they are most vulnerable to immune selection, rather than relying on post-infection recall responses that favor dominant sporozoite antigens.
2Productivity
If conventional approaches manually clone and test candidate antigens, then the process is flexible, but it is time-consuming and limited by technological bottlenecks in studying T cell responses against numerous pathogen proteins
Solution Approach 1:
The patent employs a universal antigen presentation system using transgenic mouse models that can simultaneously present multiple pathogen proteins through a single integrated platform. This allows the same animal model to screen for responses against dozens of different antigens without requiring separate cloning and testing procedures for each, thereby increasing throughput while managing complexity through standardized protocols.
Solution Approach 2:
The patent uses synthetic peptide copies and recombinant protein expressions as substitutes for complex live pathogen challenges. These simplified antigen preparations can be produced in large quantities through standard molecular biology techniques, enabling high-throughput screening of T cell responses against numerous pathogen proteins without the technological bottlenecks of working with live parasites or viruses.
3Reliability
If conventional vaccine development focuses on dominant antigens expressed in sporozoites, then vaccine subunits with protective efficacy are identified, but subdominant antigens that are also protective are missed
Solution Approach 1:
The patent applies local quality by tailoring the immune response assessment to specific antigen locations and expression patterns. Different assays and evaluation criteria are applied to detect responses to liver-stage antigens versus sporozoite antigens, and subdominant antigens are specifically targeted using localized immunization strategies that enhance their detectability without being overwhelmed by dominant antigen responses.
Data Source
AI summary
An immunogenic composition is provided herein. The immunogenic compositions are used to identify and select immunogenic antigens that elicit immune responses in a subject and may be subsequently used in multi-antigen vaccine compositions against one or more diseases or conditions. According to some embodiments, the immunogenic composition may include a plurality of nucleic acid fragments or minigenes derived from a nucleic acid library, wherein each nucleic acid fragment encodes a different antigen or functional portion thereof, and wherein the different antigens or functional portions thereof are associated with one or more disease or condition. The immunogenic composition may also include a delivery medium loaded with the plurality of nucleic acid fragments and in some embodiments, the delivery medium is loaded with nucleic acid fragments in such a way that individual antigen presenting cells receive only a subset of the nucleic acids within a vaccine in order to minimize antigenic competition.