Stable Staphylococcus aureus Vaccine via Lyophilization

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Solution Overview

Problem

There is an urgent need for vaccines against Staphylococcus aureus infections, particularly with enhanced antigen stability due to the structural instability of ClfA and MntC proteins, which degrade quickly, and the increasing prevalence of antibiotic-resistant strains.

Innovation Solution

A reconstituted multi-antigen immunogenic composition comprising isolated S. aureus ClfA, CP5, CP8, and MntC proteins, conjugated to carrier proteins and stabilized through lyophilization with specific buffers and bulking agents, maintaining stability and immunogenicity for extended periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ClfA and MntC proteins are used as vaccine antigens, then immunogenicity is improved, but stability deteriorates due to rapid degradation

Engineering Contradiction:
ImproveimmunogenicityVSAvoidprotein stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent combines unstable protein antigens (ClfA and MntC) with carrier proteins and adjuvants to create a composite vaccine formulation. This composite structure protects the unstable proteins from degradation while maintaining their immunogenicity, resolving the contradiction between immunogenicity and stability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

Carrier proteins serve as intermediaries that bind to and stabilize the unstable ClfA and MntC antigens. The carrier proteins act as protective mediators that prevent degradation of the target antigens while still allowing them to elicit immune responses.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If protein antigens are formulated for vaccination, then immunogenicity is improved, but storage stability deteriorates over time

Engineering Contradiction:
ImproveimmunogenicityVSAvoidstorage stability
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent modifies formulation parameters by adjusting pH, adding stabilizing agents, and optimizing protein concentrations to extend the storage stability of the vaccine antigens. These parameter changes allow the proteins to maintain both immunogenicity and stability during storage.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The vaccine formulation is designed to maintain continuous stability and immunogenicity over extended storage periods. The formulation system ensures that the antigens remain stable and functional throughout the shelf life, enabling continuous useful action without degradation.

Inventive Principle:
Principle #20Continuity of useful action

3Reliability

If multiple antigen components are combined, then immunogenicity is improved, but formulation complexity increases

Engineering Contradiction:
ImproveimmunogenicityVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple antigen components (ClfA, MntC, and carrier proteins) into a single integrated vaccine formulation. This combining approach maintains comprehensive immunogenicity while simplifying the overall formulation structure and administration.

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 composition effectively induces an immune response, preventing or reducing the severity of Staphylococcal infections by maintaining the stability and immunogenicity of ClfA and MntC proteins, addressing the challenge of antigen degradation and antibiotic resistance.

Implementation Method 1

stabilized through lyophilization with specific buffers and bulking agents

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Data Source

PatentEP3150222B1Stable immunogenic compositions of staphylococcus aureus antigens
Publication Date: 2019.11.27 WYETH LLC
  • EP3150222B1 patent drawingFigure 1
  • EP3150222B1 patent drawingFigure 2A
  • EP3150222B1 patent drawingFigure 2B

AI summary

The present invention is directed towards a lyophilized or reconstituted multi-antigen or multicomponent immunogenic composition comprising antigens from a staphylococcal bacterium. The antigens, which are polypeptides and polysaccharides, may be obtained, inter alia, directly from the bacterium using isolation procedures, or they may be produced using synthetic protocols, or they may be recombinantly produced using genetic engineering procedures, or through a combination of any of the foregoing.