Dried Thermostable Vaccine Compositions With Trehalose Stabilization

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Solution Overview

Problem

Current aluminum-salt adjuvants in vaccines face limitations such as stability issues during storage, require narrow temperature ranges, are relatively weak immunogens, do not foster cellular immunity, and may induce non-neutralizing antibodies, with lyophilization leading to potency loss due to particle aggregation and degradation of recombinant proteins.

Innovation Solution

Development of dried vaccine compositions bound to adjuvant and containing immunostimulatory molecules, using trehalose to prevent particle aggregation and optimize binding conditions, combined with immunostimulatory molecules like CpG DNA, flagellin, and Monophosphoryl Lipid A (MPL) to enhance immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aluminum-salt adjuvants are used to enhance immunogenicity, then antibody titers are elevated, but vaccine stability deteriorates due to narrow temperature storage ranges and inability to be frozen

Engineering Contradiction:

ImproveimmunogenicityVSAvoidstorage stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the physical state parameter of the vaccine from liquid to dried/powder form through lyophilization. This parameter change enables the vaccine to be stored at room temperature (20-25°C) for extended periods without refrigeration, fundamentally improving storage stability while maintaining immunogenicity through the preserved adjuvant-antigen complex structure

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite dried vaccine composition containing aluminum-salt adjuvant particles with adsorbed antigen, stabilized by lyophilization technology. The composite structure maintains the immunogenic benefits of aluminum adjuvants while adding thermal stability through the dried matrix formulation

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If lyophilization is performed to improve storage stability, then temperature range is expanded, but potency is lost due to particle aggregation and protein degradation

Engineering Contradiction:

Improvestorage stabilityVSAvoidpotency

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent applies preliminary protective action by incorporating stabilizers and optimizing formulation conditions before lyophilization. The antigen is pre-adsorbed onto aluminum adjuvant particles under controlled conditions, and protective excipients are added to prevent aggregation during the freezing and drying processes, ensuring potency is maintained

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses stabilizing excipients as intermediary substances that protect the antigen-adjuvant complex during lyophilization. These intermediaries prevent direct harmful interactions between the antigen and harsh processing conditions, maintaining structural integrity and immunogenicity through the drying process

Inventive Principle:

Principle #24Intermediary (Mediator)

3Ease of manufacture

If traditional aluminum-salt adjuvants are used, then manufacturing is simple, but cellular immunity is not fostered and non-neutralizing antibodies are induced

Engineering Contradiction:

Improvemanufacturing simplicityVSAvoidimmune response quality

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent merges traditional aluminum-salt adjuvants with novel immunostimulatory molecules (such as TLR agonists, cytokines, or other adjuvant components) to create a combined adjuvant system. This combination maintains the ease of manufacturing with aluminum salts while adding the capability to foster cellular immunity and induce neutralizing antibodies through the additional immunostimulatory components

Inventive Principle:

Principle #5Merging (Combining)

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 solution provides stable, thermally resistant vaccines with enhanced immunogenicity, promoting both humoral and cellular immunity, and overcoming the limitations of traditional aluminum-salt adjuvants by maintaining particle size and structure integrity during lyophilization.

Implementation Method 1

lyophilizing the frozen vaccine formulation to create a dried vaccine composition

Methodology Applied

Scientific EffectLyophilization: Freeze Drying

Implementation Method 2

using trehalose to prevent particle aggregation and optimize binding conditions

Methodology Applied

Scientific EffectParticle aggregation prevention:

Implementation Method 3

This adsorption is typically facilitated through electrostatic interactions between the antigen and adjuvant

Methodology Applied

Scientific EffectElectrostatic interactions: Electrostatics

Implementation Method 4

antigens must be adsorbed on the surface of the adjuvant

Methodology Applied

Scientific EffectAdsorption: Adsorption

Implementation Method 5

freezing the liquid vaccine formulation to create a frozen vaccine formulation

Methodology Applied

Scientific EffectFreezing: Freezing

Data Source

PatentUS12447127B2Thermostable vaccine compositions and methods of preparing the same

Publication Date: 2025.10.21 THE REGENTS OF THE UNIVERSITY OF COLORADO

AI summary

The present invention relates generally to the field of immunogenic compositions containing volatile salts. In certain embodiments, compositions and methods disclosed herein relate to producing and using novel combinations to create frozen immunogenic agents bound to adjuvant having improved formulations and improved consistency of distribution of adjuvant for storage and subsequent delivery to a subject in need thereof.