Shingles Vaccine Composition Using CpG Adjuvant to Lower Reactogenicity
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Solution Overview
Problem
Existing shingles vaccines, such as SHINGRIX®, have a high reactogenicity profile, leading to significant adverse events, which can impact compliance with the recommended two-dose regimen, while maintaining effective immunogenicity against varicella zoster virus (VZV).
Innovation Solution
An immunogenic composition comprising a varicella zoster virus surface glycoprotein E (gE) antigen combined with a toll-like receptor 9 (TLR9) agonist, specifically an unmethylated cytidine-phospho-guanosine (CpG) oligonucleotide, is used to stimulate an immune response, potentially reducing adverse effects while maintaining or improving immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If AS01B adjuvant is used to improve immunogenicity, then immune response against VZV is enhanced, but reactogenicity and adverse events increase significantly
Solution Approach 1:
The patent changes the adjuvant parameter from AS01B (lipid A + saponin) to CpG 1018 (TLR9 agonist oligonucleotide), fundamentally altering the immunological mechanism while maintaining immunogenicity. This parameter substitution resolves the contradiction by selecting an adjuvant with different side effect profiles.
Solution Approach 2:
The patent employs a synthetic oligonucleotide adjuvant (CpG 1018) that can be produced more simply and with fewer severe side effects compared to the complex liposomal AS01B formulation. This shorter-lived, simpler adjuvant achieves the desired immunogenic effect without the persistent reactogenicity of AS01B.
2Reliability
If high immunogenicity vaccine is administered, then protection against shingles is improved, but compliance with two-dose regimen decreases due to severe adverse events
Solution Approach 1:
By changing the adjuvant parameter to CpG 1018, the patent reduces the severity of adverse events while preserving immunogenicity, thereby improving patient compliance with the recommended two-dose regimen without sacrificing protection efficacy.
3Quantity of substance
If AS01B adjuvant system is used, then antibody response is enhanced, but local and systemic reactogenicity increases
Solution Approach 1:
The patent substitutes the AS01B adjuvant system with CpG 1018, changing the immunological parameter from a liposomal saponin-based system to a TLR9-agonist oligonucleotide. This parameter change maintains or enhances antibody response while significantly reducing local and systemic reactogenicity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition effectively stimulates a robust immune response against VZV with reduced reactogenicity, enhancing safety and compliance by minimizing severe adverse events.
Implementation Method 1
toll-like receptor 9 (TLR9) agonist, wherein the TLR9 agonist is an oligonucleotide of from 10 to 35 nucleotides in length comprising an unmethylated cytidine-phospho-guanosine (CpG) motif
Data Source
AI summary
The present disclosure relates to immunogenic compositions comprising a varicella zoster vims (VZV) glycoprotein E antigen and a toll-like receptor 9 (TLR9) agonist, such as an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for stimulating an immune response against VZV in an individual in need thereof.