CpG Adjuvanted Herpes Zoster Vaccine Reducing Reactogenicity

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Solution Overview

Problem

There is an unmet medical need for an herpes zoster vaccine with a superior safety profile, as existing vaccines like SHINGRIX® have high levels of severe side effects and ZOSTAVAX® has been associated with adverse reactions.

Innovation Solution

The development of an immunogenic composition comprising a VZV glycoprotein E antigen and an oligonucleotide containing an unmethylated CpG motif, which is administered to increase cell-mediated immunity against varicella zoster virus, thereby preventing herpes zoster and postherpetic neuralgia.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If SHINGRIX® vaccine is used to prevent herpes zoster, then efficacy against herpes zoster and postherpetic neuralgia is improved, but severe side effects and reactogenicity increase

Engineering Contradiction:

Improveefficacy against herpes zosterVSAvoidsevere side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the adjuvant composition parameters by replacing AS01B with CpG 1018® adjuvant, changing the immunostimulatory mechanism from TLR4/TLR2 agonism to TLR9 agonism. This parameter change in the adjuvant system maintains vaccine efficacy while reducing severe reactogenicity events

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces CpG 1018® adjuvant as an intermediary substance that mediates the immune response to the VZV gE antigen. This intermediary adjuvant provides a different immunological pathway that achieves protective immunity with a more favorable safety profile compared to AS01B

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If ZOSTAVAX® vaccine is used to prevent herpes zoster, then vaccination coverage is improved, but adverse reactions and safety concerns increase

Engineering Contradiction:

Improvevaccination coverageVSAvoidadverse reactions

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a recombinant protein subunit vaccine (VZV gE) rather than a live attenuated virus, creating a safer vaccine platform that can be administered widely without the long-term safety concerns associated with live vaccines in immunocompromised or elderly populations

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent creates a composite vaccine formulation combining VZV gE antigen with CpG 1018® adjuvant, merging the safety advantages of recombinant subunit technology with the immunogenicity enhancement of CpG oligonucleotide adjuvant to achieve both high coverage and safety

Inventive Principle:

Principle #40Composite materials

3Reliability

If adjuvant is added to increase immune response, then immunogenicity is improved, but reactogenicity and severe events increase

Engineering Contradiction:

ImproveimmunogenicityVSAvoidreactogenicity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the adjuvant parameter from AS01B (containing MPL and QS-21) to CpG 1018® (a phosphorothioate-modified oligodeoxynucleotide), which activates TLR9 instead of TLR4. This parameter change in adjuvant mechanism reduces severe reactogenicity while maintaining immunogenicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality modification by using phosphorothioate backbone modification in the CpG oligonucleotide, which enhances stability and immunogenicity at the molecular level while controlling the overall reactogenicity profile of the vaccine formulation

Inventive Principle:

Principle #3Local quality

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 immunogenic composition effectively stimulates an immune response, increasing cell-mediated immunity and humoral immunity against VZV, thereby reducing the risk of developing herpes zoster and postherpetic neuralgia, with a potentially improved safety profile compared to existing vaccines.

Implementation Method 1

the TLR9 agonist is an oligonucleotide of from 8 to 35 nucleotides in length comprising an unmethylated cytidine-phospho-guanosine (CpG) motif

Methodology Applied

Scientific EffectToll-like receptor 9 activation:

Data Source

PatentUS20250163105A1Immunogenicity of a cpg-adjuvanted herpes zoster vaccine

Publication Date: 2025.05.22 DYNAVAX TECHNOLOGIES CORPORATION

AI summary

The present disclosure relates to methods for increasing cell-mediated immunity against varicella zoster virus (VZV) in a human subject in need thereof by administration of an immunogenic composition comprising effective amounts of a VZV glycoprotein E antigen and an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for prevention of herpes zoster and/or postherpetic neuralgia.