Simian Adenoviral Vector Encoding RSV Antigens

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Solution Overview

Problem

Current vaccines and treatments for respiratory syncytial virus (RSV) are inadequate, with no licensed vaccine available and existing treatments being costly, difficult to administer, and having safety concerns, while also failing to provide full protective immunity, leading to frequent re-infections throughout life.

Innovation Solution

Development of a recombinant adenoviral vector based on simian adenoviruses, specifically a chimpanzee adenovirus with two expression cassettes encoding RSV antigenic proteins or fragments, such as RSV F, M, and N antigens, to induce an immune response and provide immunity against RSV.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If human adenoviral vectors are used for gene transfer, then transgene delivery efficiency is high, but pre-existing immunity reduces effectiveness

Engineering Contradiction:

Improvetransgene delivery efficiencyVSAvoideffectiveness due to pre-existing immunity

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The invention uses simian adenovirus vectors instead of human adenovirus vectors to deliver RSV antigens. Simian adenoviruses are not commonly encountered by humans, so pre-existing immunity is minimal or absent, allowing effective gene transfer and antigen expression without neutralizing antibodies blocking infection

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention changes the viral vector type from human adenovirus to simian adenovirus, fundamentally altering the immunological parameters. This parameter change allows the vector to evade pre-existing human immunity while maintaining efficient transgene delivery capability

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If single antigen vaccines are used, then vaccine development is simple, but immune response coverage is limited

Engineering Contradiction:

Improvevaccine development complexityVSAvoidimmune response coverage

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The invention combines multiple RSV antigen genes (F, G, M, N, and L genes) into a single simian adenovirus vector construct. This merging approach allows simultaneous expression of multiple viral antigens from one vaccine, providing broad immune response coverage while maintaining a single vaccine administration

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The simian adenovirus vector serves multiple functions: it acts as a delivery vehicle for multiple RSV antigen genes, provides strong expression promoters (CMV and RSV promoters), and elicits comprehensive immune responses against multiple RSV proteins simultaneously

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Object-affected harmful factors

If replication defective adenoviruses are used, then safety is improved, but transgene payload amplification is lost

Engineering Contradiction:

ImprovesafetyVSAvoidtransgene payload amplification

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The invention uses replication-defective simian adenovirus vectors that cannot replicate in human cells, ensuring safety. The vectors deliver their transgene payload once and then are effectively discarded by the cell's immune mechanisms, avoiding the risks of replication-competent viruses while still providing sufficient antigen expression for vaccine efficacy

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Data Source

PatentUS11859199B2Adenoviral vectors with two expression cassettes encoding RSV antigenic proteins or fragments thereof

Publication Date: 2024.01.02 GLAXOSMITHKLINE BIOLOGICALS SA

AI summary

An adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, and wherein each transgene encodes an RSV antigenic protein or a fragment thereof.