Modified CMV VLP Compositions for Stable Canine IL-1β Antigen Display
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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 clinical trial testing, product registration, and commercial supply, particularly under varying conditions of temperature and ionic strength.
Innovation Solution
Development of modified CMV VLPs with specific canine Interleukin-1β mutein antigens linked via covalent bonds, incorporating consecutive negative amino acids, which enhance stability and prevent aggregation, allowing scalable manufacturing through ion-exchange chromatography.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional VLP platforms are used to present antigens, then immunogenicity is achieved, but stability and aggregation control deteriorate under varying temperature and ionic strength conditions
Solution Approach 1:
The patent modifies the VLP platform by changing the amino acid sequence of the coat protein, specifically introducing charged residues (lysine or arginine) at positions 83 and/or 84 of the CMV coat protein. This parameter change in the molecular structure enhances electrostatic interactions and improves stability under varying temperature and ionic strength conditions while preventing aggregation.
Solution Approach 2:
The invention creates a composite VLP structure by combining modified CMV coat protein subunits with antigenic determinants. The modified coat protein forms a stable scaffold that presents antigens in a controlled manner, achieving both immunogenicity and improved stability through the composite architecture.
2Reliability
If VLP based vaccines are developed for clinical applications, then immunogenicity is improved, but aggregation occurs which is unacceptable for GMP products
Solution Approach 1:
By modifying the charge distribution on the VLP surface through specific amino acid substitutions in the coat protein, the patent changes the physical-chemical parameters that govern protein-protein interactions. This prevents unwanted aggregation while preserving the immunogenic properties of the VLP platform.
3Reliability
If VLP platforms are used for vaccine development, then immunogenicity is achieved, but manufacturability and scalability are limited
Solution Approach 1:
The modified coat protein with enhanced stability properties enables simpler purification protocols and better process control during manufacturing. The structural modifications facilitate scalable production while maintaining high immunogenicity, addressing the manufacturability challenge.
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-cIL-1β conjugates maintain structural integrity and immunogenicity, inducing high titers of neutralizing antibodies with minimal adverse effects, while being stable under elevated temperatures and higher ionic strengths, facilitating efficient production and product registration.
Implementation Method 1
Virus-like particles (VLPs) have become an established and accepted vaccine technology, in particular as immunological carriers for inducing strong immune responses against conjugated antigens
Implementation Method 2
the specific insertion of these stretches of consecutive negative amino acids lead to improvements in stability of the resulting modified CMV VLPs as compared to prior art CMV VLPs under conditions of elevated temperatures and higher ionic strengths
Implementation Method 3
allowing scalable manufacturing through ion-exchange chromatography
Data Source
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 comprise a stretch of consecutive negative amino acids selected from aspartic acid and/or glutamic acid to which canine Interleukin-1β mutein antigens, cIL-1β-D145X antigens, are linked, as well as pharmaceutical compositions thereof, which compositions preferably serve as vaccines for generating immune responses, in particular antibody responses, against cIL-1β.