Glycoengineered Outer Membrane Vesicles for Gram-Positive Vaccines

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Solution Overview

Problem

Current vaccines for Gram-positive bacteria do not utilize outer membrane vesicles (OMVs) as they do not produce OMVs, and there is a need for alternative OMV vaccines, especially against Gram-positive bacteria like Streptococcus pneumoniae.

Innovation Solution

Glycoengineered outer membrane vesicles (geOMVs) are produced by genetically engineering Gram-negative bacteria to express heterologous glycans, such as O antigens or capsular polysaccharides from Gram-positive bacteria, which are incorporated into the lipopolysaccharides, allowing the geOMVs to elicit an immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If Gram-negative bacteria are genetically engineered to express heterologous glycans from Gram-positive bacteria, then the ability to create vaccines against Gram-positive bacteria is improved, but the complexity of vaccine manufacturing increases

Engineering Contradiction:

Improvevaccine applicabilityVSAvoidmanufacturing complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

Gram-negative bacteria serve as an intermediary host system to produce heterologous glycans from Gram-positive bacteria. The engineered bacteria express foreign glycosyltransferase genes and acceptor substrates, converting them into OMVs displaying the desired Gram-positive bacterial antigens, thereby bridging the gap between Gram-positive pathogens and Gram-negative vaccine platforms

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The OMV platform is made universal by enabling it to display diverse heterologous glycans from different Gram-positive bacteria through genetic engineering. A single Gram-negative bacterial host system can be adapted to produce vaccines against multiple different pathogens by introducing different glycosyltransferase genes and acceptor substrates

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If heterologous glycans are incorporated into lipopolysaccharides of OMVs, then immune response induction is improved, but the difficulty of controlling glycan structure increases

Engineering Contradiction:

Improveimmune responseVSAvoidglycan structure control

Core Design Contradiction:

ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The acceptor substrate is pre-modified with a specific sugar residue (e.g., GalNAc) before the glycosyltransferase reaction occurs. This preliminary modification ensures that the heterologous glycan is built upon a known, controlled foundation, facilitating better structural predictability and characterization of the final OMV antigen

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The glycosyltransferase enzyme is engineered or selected to exhibit substrate specificity that ensures heterologous glycans are attached only to specific acceptor substrates at defined locations on the LPS molecule. This localized and specific modification maintains structural control while enabling diverse antigen display

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS9526775B2Glycoengineered outer membrane vesicles and use thereof as vaccines

Publication Date: 2016.12.27 THE GOVERNORS OF THE UNIV OF ALBERTA

AI summary

The present application relates to glycoengineered outer membrane vesicles obtained from recombinant, gram-negative bacteria comprising hetereologous DNA encoding an enzyme or enzymes that produce a heterologous glycan that replaces all or a portion of the naturally-occurring O antigen in the lipopolysaccharides of the bacteria. Also provided by the present application are immunogenic compositions and vaccines prepared from the glycoengineered outer membrane vesicles expressing the heterologous glycans at their surface.