Modified CMV VLP-NGF Conjugates for Aggregation-Free Vaccines

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Solution Overview

Problem

Existing virus-like particle (VLP) based vaccines face challenges in stability, aggregation, and manufacturability, which are critical for product registration and market launch, particularly when linking nerve growth factor (NGF) antigens, leading to undesirable aggregation and precipitation.

Innovation Solution

Incorporating consecutive negative amino acids, such as aspartic acid or glutamic acid, into the CMV VLPs to enhance stability and prevent aggregation, allowing for scalable manufacturing through ion-exchange chromatography and maintaining structural integrity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If NGF antigens are linked to CMV VLPs using chemical linker coupling technology, then immune response is enhanced, but aggregation and precipitation occur

Engineering Contradiction:

Improveimmune responseVSAvoidaggregation and precipitation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent modifies the surface charge parameters of CMV VLPs by incorporating stretches of consecutive negative amino acids (aspartic acid or glutamic acid) at positions 75-85 of the coat protein sequence. This parameter change creates negative charged attachment sites that covalently link NGF antigens through amide bonds, enhancing immune response while preventing aggregation and precipitation that occurs with conventional chemical linker coupling methods

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If conventional chemical linker coupling is used to present antigens on VLP surface, then antigen presentation is achieved, but stability under elevated temperatures and ionic strengths deteriorates

Engineering Contradiction:

Improveantigen presentationVSAvoidstability under elevated temperatures and ionic strengths

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical and physical parameters of the VLP surface by introducing negative charged amino acid stretches, creating stable attachment sites for antigens. This modification maintains structural integrity and stability under elevated temperatures and ionic strengths while achieving effective antigen presentation, overcoming the limitations of conventional chemical linker coupling

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structure by integrating foreign amino acid sequences (stretches of aspartic acid or glutamic acid) into the native CMV coat protein sequence. This composite polypeptide structure combines the self-assembly properties of viral proteins with the stability and antigen-binding capabilities of engineered charge regions, achieving both ease of manufacture and enhanced stability

Inventive Principle:

Principle #40Composite materials

3Ease of manufacture

If additional negative charges are included in VLP-forming proteins to link antigens, then antigen coupling is enabled, but VLP formation is adversely affected

Engineering Contradiction:

Improveantigen couplingVSAvoidVLP formation

Core Design Contradiction:

Ease of manufactureVSStrength

Solution Approach 1:

The patent applies local quality modification by introducing stretches of consecutive negative amino acids specifically at positions 75-85 of the coat protein sequence, rather than uniformly throughout the protein. This localized modification enables antigen coupling through negative charge interactions while preserving the overall self-assembly and structural integrity of the VLP formation process

Inventive Principle:

Principle #3Local quality

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 modified CMV VLP-NGF conjugates retain stability and immunogenicity, preventing aggregation and facilitating scalable production, ensuring product quality for clinical trials and market readiness.

Implementation Method 1

the improved stability in higher salt solution arising from the surface charge modifications to the CMV VLPs is additionally beneficial or even essential for its processability and purification by ion-exchange chromatography, in particular anion exchange chromatography

Methodology Applied

Scientific EffectIon-exchange chromatography: Ion Exchange

Implementation Method 2

the inventive CMV VLP-NGF conjugates did not form aggregates and remained stable in solution upon linking NGF antigens, while prior art CMV VLPs formed large aggregates and precipitated upon such linking

Methodology Applied

Scientific EffectElectrostatic repulsion: Ion Repulsion/Attraction

Data Source

PatentUS20260069668A1Veterinary compositions of modified virus-like particles of CMV and NGF antigens

Publication Date: 2026.03.12 SAIBA ANIMAL HEALTH AG

AI summary

The present invention relates to compositions comprising modified virus-like particles (VLPs) of Cucumber Mosaic Virus (CMV), and in particular to modified VLPs of CMV comprising chimeric CMV polypeptides which comprises a stretch of consecutive negative amino acids selected from aspartic acid or glutamic acid to which nerve growth factor (NGF) antigens are linked as well as pharmaceutical compositions thereof, which compositions preferably serve as vaccine platform for generating immune responses, in particular antibody responses, against said NGF antigens linked to the modified CMV VLPs.