Multimeric RSV Gcc Polypeptides Addressing Weak Immunogenicity

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Solution Overview

Problem

Current vaccines for respiratory syncytial virus (RSV) face challenges due to safety concerns and weak immune responses, with existing technologies failing to elicit sufficient efficacy, particularly in adults, and the Gcc region of RSV G being a poor immunogen due to its small size and hypervariable regions.

Innovation Solution

Development of antigenic RSV G polypeptides comprising more than two RSV Gcc monomers, which can be presented as multimers without ferritin, utilizing a multimerization domain like foldon to form particles such as trimers, tetramers, or hexamers, to enhance immunogenicity and elicit a robust immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If the Gcc region of RSV G is used as a vaccine antigen, then the antigen is smaller and easier to manufacture, but it is a poor immunogen due to its small size and hypervariable regions

Engineering Contradiction:

Improveease of manufactureVSAvoidimmunogenicity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent merges multiple Gcc monomers (at least two, preferably three or more) into a single multimeric polypeptide chain. This combining approach increases the overall size and immunogenicity of the antigen while maintaining the manufacturability of a single polypeptide construct, directly resolving the contradiction between small size/ease of manufacture and poor immunogenicity

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent segments the Gcc region from the hypervariable regions of the full G protein, isolating only the conserved central region (amino acids 151-193) for inclusion in the multimeric construct. This segmentation eliminates immune-distracting hypervariable regions while preserving the conserved epitopes, thereby improving immunogenicity without compromising ease of manufacture

Inventive Principle:

Principle #1Segmentation

2Reliability

If existing RSV vaccines are used, then they have been available for decades, but they carry safety concerns and stimulate only short-lived, weak immune responses

Engineering Contradiction:

ImprovesafetyVSAvoidduration of immune response

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the structural parameters of the antigen by creating multimeric polypeptides with multiple Gcc monomers linked in a defined architecture. This parameter change (from monomeric to multimeric) enhances the stability and persistence of the immune response while maintaining safety, as the construct uses only conserved regions without live virus components

Inventive Principle:

Principle #35Parameter changes

3Reliability

If RSV F antigen in post-fusion conformation is used, then it has been tested in clinical programs, but it failed to elicit sufficient efficacy in adults

Engineering Contradiction:

ImproveefficacyVSAvoidcomplexity of antigen structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the essential immunogenic elements (conserved Gcc epitopes) from the complex full-length G protein and RSV F antigen, creating a simplified multimeric construct that focuses immune recognition on conserved regions. This extraction approach achieves efficacy in adults by targeting conserved epitopes while reducing structural complexity compared to full-length proteins

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12454553B2Antigenic multimeric respiratory syncytial virus polypeptides

Publication Date: 2025.10.28 SANOFI SA(FR)

AI summary

This disclosure relates to antigenic multimeric respiratory syncytial virus (RSV) G polypeptides for use in eliciting an immune response to RSV.