Antigen Adjuvant Binding via Phosphate Groups

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current subunit vaccines, particularly those using aluminum hydroxide as an adjuvant, induce relatively weak immune responses due to antigen desorption and in vivo clearance, necessitating the development of more stable and immunogenic antigen-adjuvant complexes.

Innovation Solution

The introduction of a Region of Repetitive Carboxylic Groups (RRC) or Repetitive Lysyl/Guanidino Groups (RRL) into antigen polypeptides to enhance electrostatic interactions with adjuvants like aluminum hydroxide, stabilizing antigen binding and controlling orientation for improved immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If aluminum hydroxide is used as an adjuvant in subunit vaccines, then safety and ease of production are improved, but immune response strength deteriorates due to antigen desorption and clearance

Engineering Contradiction:

Improveease of productionVSAvoidimmune response strength

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The invention modifies the antigen's chemical properties by introducing phosphate groups at specific N-terminal positions, changing its binding affinity parameters to alum. This parameter change enables stronger and more stable interaction between the antigen and adjuvant, resolving the contradiction between ease of manufacture and immune response strength

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

Phosphate groups serve as intermediary binding sites that mediate the interaction between the antigen and alum adjuvant. These phosphate groups act as a bridge, facilitating stronger electrostatic and ligand exchange interactions with the aluminum hydroxide surface, thereby enhancing antigen retention and immune response

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If antigens are adsorbed to alum adjuvant, then vaccine production is simplified, but antigen stability deteriorates due to desorption in interstitial fluid or serum

Engineering Contradiction:

Improvevaccine production simplicityVSAvoidantigen stability

Core Design Contradiction:

Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The invention changes the chemical parameters of the antigen by adding N-terminal phosphate groups, which fundamentally alters its binding characteristics to alum. This parameter modification increases binding affinity and stability, preventing desorption in physiological conditions while maintaining simple vaccine production processes

Inventive Principle:

Principle #35Parameter changes

3Stability of the object's composition

If C-terminal cysteine residues are used to anchor antigen on alum, then binding stability is improved, but antibody response orientation deteriorates by shifting away from the base of the antigen

Engineering Contradiction:

Improvebinding stabilityVSAvoidantibody response orientation

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

Instead of anchoring the antigen at the C-terminal end (conventional approach), the invention inverts the anchoring strategy by placing phosphate groups at the N-terminal positions. This inversion allows the antigen to bind stably to alum while maintaining proper orientation of the antigenic determinants, thereby improving both binding stability and antibody response quality

Inventive Principle:

Principle #13The other way round (Inversion)

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

This approach increases humoral antibody responses and neutralization potency by maintaining antigen accessibility and stability on the adjuvant surface, leading to enhanced immunogenicity and broader protective immunity.

Implementation Method 1

Methodology Applied

Scientific EffectElectrostatic interactions: Electrostatics

Implementation Method 2

Alum has an isoelectric point of 11 and a positive surface charge at physiological pH (7.4), which allows its attraction of negatively charged antigens through electrostatic interactions

Methodology Applied

Scientific EffectElectrostatic interactions: Electrostatics

Implementation Method 3

Aluminum has a higher affinity for phosphate than hydroxyls, and phosphates can displace hydroxyls on the surface of alum. This ligand exchange reaction affords a stronger force for antigen binding to alum

Methodology Applied

Scientific EffectLigand exchange reaction: Chemical Bonding

Data Source

PatentUS20240398929A1Engineering antigen binding to, and orientation on, adjuvants for enhanced humoral responses and immunofocusing

Publication Date: 2024.12.05 CZ BIOHUB SF LLC

AI summary

New vaccine compositions comprising a modified antigen bound to the surface of an adjuvant or carrier by electrostatic interactions are disclosed. The antigen of the vaccine composition is presented in a defined orientation on an adjuvant surface such that epitope accessibility is altered and an immune response is redirected toward specific epitopes. In some embodiments the vaccine composition comprises one or more recombinant antigen polypeptides adsorbed to an alum particle. In some embodiments, the recombinant antigen polypeptide comprises a Region of Repetitive Carboxylic Groups (RRC) or a Region of Repetitive Lysyl/Guanidino Groups (RRL).