Dengue VLP with Pre-cleaved pr-M Junction
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Solution Overview
Problem
Current dengue vaccines have limitations, including lower efficacy and restricted use in populations over 9 years old with prior dengue exposure, necessitating the development of a second-generation vaccine that can effectively neutralize multiple dengue virus serotypes.
Innovation Solution
Development of a virus-like particle (VLP) encoding a membrane protein with a pre-cleaved pr-M junction, used to produce antibodies capable of neutralizing at least two serotypes of dengue virus, combined with a pharmaceutically acceptable carrier or adjuvant to enhance immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a first-generation dengue vaccine is used, then it provides some protection, but it has lower efficacy and is limited to populations under 9 years old without prior dengue exposure
Solution Approach 1:
The vaccine is segmented into four separate viral-like particles (VLPs), each targeting a specific dengue serotype (DENV-1, DENV-2, DENV-3, DENV-4). This segmentation allows the vaccine to provide targeted protection against each serotype while maintaining overall vaccine safety and efficacy across different population groups
Solution Approach 2:
The vaccine achieves universality by incorporating all four dengue serotypes into a single vaccine formulation. The VLPs are designed with membrane proteins from different serotypes, enabling the vaccine to provide broad protection across multiple serotypes and potentially different age groups, overcoming the limitations of first-generation vaccines
2Reliability
If the membrane protein uses a wild-type pr-M junction sequence, then it maintains natural virus structure, but it fails to induce strong cross-reactive neutralizing antibodies
Solution Approach 1:
The invention applies local quality by specifically modifying only the pr-M junction region of the membrane protein while keeping the rest of the protein structure intact. The mutated pr-M junction sequences (e.g., RKERRHEGMTTCTG for DENV-2) are designed to enhance immunogenicity and cross-reactivity locally, without disrupting the overall viral-like particle structure
Solution Approach 2:
The invention changes the amino acid sequence parameters of thepr-M junction region to optimize antibody induction. By mutating specific residues in thepr-M junction (such as changing RKERR to RKSRK or other variations), the vaccine enhances the production of cross-reactive neutralizing antibodies while maintaining the functional integrity of the membrane protein
Data Source
AI summary
The present invention is related to a Dengue virus-like particle. Said Dengue virus-like particle exhibits almost-cut pr-M junction and is particularly suitable for producing antibody that recognizes all four types of Dengue virus. The present invention also provides antibody obtained by using said virus-like particle and composition comprising the same.