gE Subunit Vaccine Composition With MLA for Safer Herpes Zoster Protection
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Solution Overview
Problem
Current herpes zoster vaccines, such as Zostavax, have limitations in efficacy, safety concerns, and supply issues, particularly for immunocompromised individuals, and there is a need for a more effective and safer vaccine composition.
Innovation Solution
A vaccine composition comprising a glycoprotein E (gE) antigen of Varicella Zoster virus (VZV) with a specific amino acid sequence and monophosphoryl lipid A (MLA) is developed, optimized for high productivity and enhanced immunogenicity, potentially formulated as a liposome with additional immune adjuvants like QS-21 and CoPoP conjugates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live attenuated VZV is used as vaccine ingredient, then vaccine efficacy is achieved, but safety concerns arise for immunocompromised individuals and pregnant women
Solution Approach 1:
The vaccine is segmented into two distinct components: a subunit antigen (glycoprotein E or gIII) that provides safety by using only specific viral proteins, and an immune adjuvant (MLA) that enhances immunogenicity. This segmentation allows the vaccine to achieve efficacy without using live attenuated virus, thereby resolving the safety-efficacy contradiction for immunocompromised individuals and pregnant women.
2Object-affected harmful factors
If subunit antigens are used, then safety is improved, but vaccine efficacy decreases
Solution Approach 1:
An immune adjuvant (monophosphoryl lipid A or MLA) is introduced as an intermediary substance that bridges the gap between the safe subunit antigen and the desired strong immune response. The adjuvant enhances the immunogenicity of the subunit antigen, allowing the vaccine to achieve efficacy comparable to live attenuated vaccines while maintaining the safety advantages of subunit formulations.
3Reliability
If live attenuated VZV vaccine is used, then immune response is stimulated, but productivity is low and supply is insufficient
Solution Approach 1:
The vaccine extracts only the essential immunogenic components (glycoprotein E or gIII) from the live virus, eliminating the need to culture and attenuate entire viruses. This extraction approach simplifies manufacturing, increases productivity, and enables large-scale production to meet global supply demands while maintaining immunogenicity through the addition of MLA adjuvant.
4Reliability
If live attenuated VZV vaccine is used, then vaccine effect is achieved, but cost is high
Solution Approach 1:
The vaccine uses recombinant subunit antigens that can be produced cost-effectively through recombinant DNA technology in bacterial or mammalian expression systems. This approach replaces expensive and complex live virus attenuation and culture processes with more economical protein expression and purification methods, reducing manufacturing costs while maintaining vaccine effect through adjuvant-enhanced immunogenicity.
Data Source
AI summary
Provided are a vaccine composition for Varicella Zoster virus (VZV) including a glycoprotein E (gE) antigen of VZV and monophosphoryl lipid A (MLA), and a method of using the same. The vaccine composition according to an aspect of the invention may significantly improve a production yield by including the gE antigen having an optimized signal peptide sequence, may enhance immunogenicity by including MLA, and may further enhance the immunogenicity enhanced by MLA by further adding saponin such as QS-21, and may be prepared in a form of CoPoP liposomes so that vaccine antigens may be presented on the surface of the liposomes for better absorption by antigen-presenting cells, and vaccine efficacy may be maximized by inclusion of the vaccine antigens and immune adjuvants in a formulation. Therefore, the vaccine composition may be useful as an alternative to current vaccines in the art for prevention or treatment of VZV infection.