CMV Virus-Like Particle Platform With Universal Th Epitopes
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Solution Overview
Problem
Existing VLP-based vaccines induce variable antibody responses and often fail to elicit strong T helper (Th) cell responses, particularly in elderly and old individuals, leading to non-responsiveness and inefficient immune responses.
Innovation Solution
Modified CMV VLPs incorporating T helper cell epitopes, preferably universal Th cell epitopes, are expressed in E. coli to enhance immunogenicity and serve as a vaccine platform for antigen presentation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing VLP-based vaccines are used, then vaccine production is achieved, but T helper cell responses are weak or absent, particularly in elderly individuals
Solution Approach 1:
The patent combines VLP technology with Th cell epitopes to create a hybrid vaccine platform. The modified CMV VLPs incorporate universal Th cell epitopes (such as PADRE, TT 830-843, HBVnc 50-69) that can bind to multiple MHC class II molecules, thereby merging the antigen presentation capability of VLPs with the T helper cell activation capability of universal epitopes. This resolves the contradiction by ensuring reliable Th cell responses across different age groups.
Solution Approach 2:
The patent employs universal Th cell epitopes that can bind to multiple MHC class II molecules across different human populations. These universal epitopes (PADRE, TT 830-843, HBVnc 50-69) are designed to recognize conserved regions of MHC class II molecules, making the vaccine effective for elderly and old individuals who typically show poor Th cell responses. This universality ensures broad applicability and reliable immune activation across diverse populations.
2Adaptability or versatility
If VLPs are used as vaccine carriers, then antigen presentation is enhanced, but antibody responses remain variable and insufficient
Solution Approach 1:
The patent merges B cell epitope presentation (through VLP surface antigens) with T helper cell activation (through incorporated Th epitopes). The modified CMV VLPs display foreign antigens on their surface for B cell recognition while simultaneously presenting Th cell epitopes to activate helper T cells. This dual functionality ensures consistent and enhanced antibody responses by providing both B cell stimulation and T cell help, resolving the variability issue in antibody production.
3Reliability
If CMV VLPs are modified to include Th cell epitopes, then immune response is enhanced, but VLP structure and assembly may be compromised
Solution Approach 1:
The patent applies local quality by incorporating Th cell epitopes at specific locations on the VLP structure rather than uniformly throughout. The universal Th epitopes are fused to the CMV coat protein in controlled configurations (N-terminal fusion, C-terminal fusion, or internal insertion), allowing localized addition of immunogenic elements while preserving the overall VLP architecture and self-assembly properties.
Solution Approach 2:
The patent utilizes parameter changes by modifying the CMV coat protein sequence to include Th epitopes while maintaining key structural parameters. The modified coat protein retains sufficient sequence identity (at least 90%, preferably 95% or higher) to the wild-type CMV coat protein, ensuring proper folding, oligomerization, and VLP assembly. This controlled parameter modification allows enhanced immunogenicity without compromising structural integrity.
Data Source
AI summary
The present invention relates to virus-like particles of plant virus Cucumber Mosaic Virus (CMV), and in particular to modified VLPs of CMV comprising Th cell epitopes, in particular universal Th cell epitopes. Furthermore, these modified VLPs serve as, preferably, vaccine platform, for generating immune responses, in particular antibody responses, against antigens linked to said modified VLPs. The presence of the Th cell epitopes, in particular universal Th cell epitopes, led to a further increase in the generated immune response.