HLA Class I-Restricted Epitope Vaccine Design for CD8 T-Cell Priming

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Solution Overview

Problem

Current vaccine strategies often fail to effectively target HLA-restricted T-cell epitopes from non-virion-integral proteins, leading to inadequate CD8 T-cell responses and potential immunopathologies due to the complexity of viral lifecycle and immunoevasion mechanisms, as well as high HLA haplotype diversity.

Innovation Solution

A method to generate a vaccine composition that includes specifically selected non-virion-integral protein-derived HLA class I-restricted epitopes (HLAI-HRE) to prime CD8 T-cell responses, avoiding immunoevasion and immunopathologies by identifying and classifying immunogenic HLAI-HRE from viral pathogens and incorporating them into vaccine formulations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current vaccine strategies target whole viral open reading frames to prime neutralizing immunoglobulin responses, then B-cell driven immunity is enhanced, but HLA-restricted T-cell epitopes from non-virion-integral proteins are not effectively targeted, leading to inadequate CD8 T-cell responses

Engineering Contradiction:

ImproveCD8 T-cell response efficacyVSAvoidvaccine composition design

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates specific HLA-restricted T-cell epitopes from non-virion-integral viral proteins, separating them from whole viral open reading frames. This extraction allows the vaccine to specifically target CD8 T-cell responses without relying on whole virus approaches, directly resolving the contradiction between T-cell response efficacy and vaccine design complexity.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the viral proteome into specific HLA-restricted epitopes from non-virion-integral proteins, creating discrete antigenic targets. This segmentation enables precise targeting of CD8 T-cell responses while avoiding the complexity of whole viral formulations, addressing both the efficacy and complexity aspects of the contradiction.

Inventive Principle:

Principle #1Segmentation

2Reliability

If vaccine compositions include virion-integral protein-derived HLA-restricted epitopes to prime B-cell driven Ig responses, then neutralizing antibody production is enhanced, but harmful immunopathologies may occur due to overexuberant reactions to virally encoded proteins

Engineering Contradiction:

Improvehumoral immunityVSAvoidimmunopathologies

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by selecting epitopes from non-virion-integral proteins rather than virion-integral proteins. This localized selection targets specific antigenic determinants that are less likely to trigger harmful immunopathologies while still effectively priming CD8 T-cell responses, thus reducing harmful factors while maintaining immunity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent converts the potential harm from virion-integral protein epitopes into benefit by deliberately selecting epitopes from non-virion-integral proteins. This strategic selection avoids the harmful immunopathological responses associated with virion proteins while maintaining effective T-cell immunity, transforming a potential harm into a beneficial vaccine design approach.

Inventive Principle:

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

3Adaptability or versatility

If HLA allelic variants are considered to achieve broad population coverage, then diverse HLA-restricted epitope presentation is possible, but the high HLA haplotype diversity complicates systematic identification and selection of effective epitopes

Engineering Contradiction:

Improvepopulation coverageVSAvoidepitope selection process

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by systematically identifying and characterizing HLA-restricted epitopes from non-virion-integral proteins before vaccine formulation. This advance work includes analyzing epitope processing and presentation across different HLA alleles, creating a pre-screened set of effective epitopes that can be applied across diverse populations without repeating the complex analysis for each vaccine formulation.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent achieves universality by selecting HLA-restricted epitopes that can be effectively presented across multiple HLA alleles and populations. The selected epitopes from non-virion-integral proteins demonstrate broad binding affinity to different HLA class I molecules, enabling a single vaccine composition to provide effective CD8 T-cell responses across diverse human populations.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20230145860A1Methods to generate vaccine compositions that prime human leukocyte antigen class i restricted CD8 t-cell responses against viral non-virion-integral derived epitopes

Publication Date: 2023.05.11 GENOVIE

AI summary

Method for providing a vaccine composition capable of effectively inducing a systemic immune response and/or a localised immune response upon administration, wherein the composition comprises human leukocyte antigen class I (HLAI)-restricted epitopes selected from viral pathogen non-virion-integral proteins (non-VIP) and thus prime a CD8 T-cell response specifically directed against virally infected cells.