Bivalent Vaccine Using Conserved Epitopes for Cross-Strain Protection
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Solution Overview
Problem
Current vaccines against Hand Foot and Mouth Disease (HFMD) caused by Enterovirus-71 (EV71) and Coxsackievirus A16 (CVA16) lack cross-protection, as antibodies against one virus do not provide significant protection against the other, due to high sequence variability in the major capsid protein VP1, leading to frequent mutations and recombination events.
Innovation Solution
Development of a synthetic polypeptide epitope-based bivalent vaccine composition using conserved epitopes from EV71 and CVA16, incorporating multiple copies of epitopes from the VP1, VP2, and VP3 proteins, expressed as a recombinant sub-unit vaccine antigen construct, which induces cross-protection against diverse strains.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional vaccines targeting single virus strains are used, then they provide specific protection against that strain, but they fail to provide cross-protection against other strains due to high sequence variability in VP1 protein
Solution Approach 1:
The vaccine construct is designed to include multiple epitopes from different viral strains (EV71 and CVA16) within a single polypeptide molecule. This multi-functional design enables the vaccine to recognize and protect against multiple virus types simultaneously, overcoming the limitation of strain-specific protection while maintaining reliable immunogenicity through conserved epitope selection
Solution Approach 2:
The invention merges epitopes from EV71 VP1, VP2, and VP3 proteins along with CVA16 epitopes into a single synthetic polypeptide construct. This combination approach consolidates multiple protective elements into one vaccine antigen, enabling broad cross-protection against diverse enterovirus strains while simplifying the vaccination regimen
2Adaptability or versatility
If multiple epitopes from different viral proteins are incorporated into a single vaccine construct, then cross-protection against diverse strains is achieved, but the complexity of antigen construction and purification increases
Solution Approach 1:
The complex multi-epitope vaccine antigen is segmented into distinct functional modules: EV71 VP1 epitopes, EV71 VP2 epitopes, EV71 VP3 epitopes, and CVA16 epitopes, each separated by linker sequences. This modular segmentation facilitates rational design, simplifies the construction process through standardized assembly, and enables independent optimization of each epitope component while maintaining overall construct functionality
Solution Approach 2:
Linker sequences serve as intermediary elements between different epitope modules in the polypeptide construct. These linkers provide flexible connections that maintain the structural integrity of individual epitopes while enabling their spatial arrangement, thus simplifying the overall construct design and facilitating efficient expression and purification
Data Source
AI summary
Conserved epitopes selected from EV71 and CVA16, the two major causative agents of Hand Foot and Mouth Disease has been used to develop sub-unit bivalent vaccine antigen construct. The said vaccine described in this invention is capable to provide cross-protection to diverse EV71 and CVA16 infection causing strains. Further disclosed are the expression of the multi-epitope vaccine antigen coding gene and the purification process involved thereof. This present invention also discloses vaccine formulations against Hand Foot and Mouth Disease and other enterovirus infections comprising the recombinant vaccine antigen construct of the present invention.