Modified HSV gD Protein Vaccine Epitope Engineering
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Solution Overview
Problem
Current antiviral drugs for HSV cannot completely eliminate the virus, leading to reactivation upon drug cessation, and there is a lack of effective vaccines for preventing infection or treating recurrence.
Innovation Solution
Development of modified HSV gD proteins through comprehensive B cell and T cell epitope analysis to enhance neutralizing antibody induction, involving de-epitoping of deleterious epitopes and addition of promiscuous T cell epitopes to induce immune refocusing and improve vaccine efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional vaccines or pathogen infection history are used, then immune response is obtained, but protective immunity is insufficient and does not differ significantly from natural infection
Solution Approach 1:
The patent applies local quality by modifying specific epitopic regions of the gD protein while preserving other regions. The gD protein is engineered to have enhanced neutralizing epitopes (such as the Nectin-1 binding site) while removing or reducing decoy epitopes that do not contribute to protective immunity. This localized modification approach ensures that the vaccine induces strong protective immunity without requiring complete pathogen inactivation or live virus use.
Solution Approach 2:
The patent employs parameter changes by altering the immunogenic properties of the gD protein through amino acid substitutions, deletions, or additions in specific epitopic regions. These modifications change the protein's ability to induce neutralizing antibodies while maintaining its structural integrity and receptor-binding capability. The modified gD protein exhibits enhanced immunogenicity parameters compared to wild-type gD.
2Reliability
If wild-type HSV gD is used for vaccine development, then immune response is induced, but neutralizing antibody levels and activity are insufficient
Solution Approach 1:
The patent enhances local quality by specifically modifying the epitopic regions of gD that are critical for neutralizing antibody induction. The Nectin-1 binding site and other neutralizing epitopes are optimized through amino acid modifications to increase their immunogenicity. Meanwhile, decoy epitopes that divert immune response away from protective antibodies are removed or reduced, thereby concentrating the immune response on neutralizing targets.
Solution Approach 2:
The patent converts the harmful effect of decoy epitopes (which induce non-neutralizing antibodies) into a benefit by deliberately removing or modifying these regions. By eliminating the decoy effect, the vaccine design ensures that the immune system focuses on generating high levels of neutralizing antibodies against critical viral entry sites, thereby converting a previously harmful immunological distraction into a beneficial focused immune response.
3Ease of operation
If HSV infects host cells through receptor association, then viral entry is achieved, but immune evasion through immunoediting system occurs
Solution Approach 1:
The patent applies the extraction principle by isolating and removing the decoy epitopic regions from the gD protein that are responsible for immune evasion through the immunoediting system. By taking out these harmful regions while retaining the essential receptor-binding domains (such as Nectin-1, HVEM, or PDGFRα binding sites), the vaccine induces immune responses that target the critical entry mechanisms without being distracted by immune-evasive decoys.
Solution Approach 2:
The patent segments the gD protein into functional domains: essential receptor-binding regions that mediate viral entry and decoy epitopic regions that facilitate immune evasion. By segmenting and selectively modifying these regions, the vaccine preserves viral entry functionality while eliminating immune evasion capabilities. The modified gD protein maintains its ability to bind host receptors but lacks the decoy epitopes that would otherwise protect the virus from neutralizing antibodies.
Data Source
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Figure 3(A)~3(B)
AI summary
The modified HSV gD protein of the present invention is a modified protein of a herpes simplex virus (HSV) envelope glycoprotein D (gD), wherein the modified HSV gD protein is derived from a wild-type HSV gD by modification of at least one of B cell epitopes having low or no neutralizing antibody-inducing activity compared to a B cell epitope present in a receptor-binding domain (RBD) (decotopes) in the ectodomain of the wild-type HSV gD, so that the modified epitope does not function as an epitope.