Paramyxovirus F Protein Stabilization for Vaccine Efficacy

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Solution Overview

Problem

Current vaccines for leading causes of lower respiratory tract infections, such as RSV, hMPV, and PIV, have not been proven safe and effective in preventing infection and reducing disease severity in humans.

Innovation Solution

Development of immunogenic compositions containing recombinant F protein antigens from RSV, hMPV, and PIV, stabilized in the trimeric prefusion conformation, combined with adjuvants to elicit a Th1 biased immune response, which are administered to elicit protection against multiple paramyxoviruses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional vaccines are used to prevent respiratory infections, then vaccine development is pursued, but safety and effectiveness have not been proven

Engineering Contradiction:

Improvevaccine safety and effectivenessVSAvoidvaccine development status

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent modifies the F protein antigen by stabilizing it in the prefusion conformation through specific structural changes and constrainment, altering its immunogenic parameters to elicit more effective neutralizing antibodies while maintaining safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The vaccine composition combines multiple paramyxovirus F protein antigens (RSV, hMPV, PIV) in a single formulation, creating a composite vaccine that provides broad protection against multiple respiratory pathogens simultaneously

Inventive Principle:

Principle #40Composite materials

2Reliability

If F protein antigens are used to elicit immune response, then protection against infection is achieved, but the antigens must be stabilized in specific conformation

Engineering Contradiction:

Improveprotective immune responseVSAvoidantigen conformational stability

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies structural modifications to the F protein including constrainment to specific conformations and modification of glycosylation sites to optimize the antigen's structural parameters for effective immune response while ensuring manufacturing feasibility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces heterologous trimerization domains at specific locations in the F protein structure to stabilize the prefusion conformation locally, while maintaining the overall functionality and immunogenicity of the antigen

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If combination vaccine is developed to cover multiple viruses, then broad protection is provided, but formulation complexity increases

Engineering Contradiction:

Improvemulti-virus protectionVSAvoidvaccine formulation complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent creates a universal vaccine formulation that targets multiple paramyxoviruses (RSV, hMPV, PIV) with a single combination product, allowing one vaccine to provide protection against several respiratory pathogens rather than requiring separate vaccines for each virus

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS8889146B2Vaccine

Publication Date: 2014.11.18 GLAXOSMITHKLINE BIOLOGICALS SA

AI summary

The present disclosure provides immunogenic compositions that include at least two paramyxovirus F protein antigens selected from human metapnuemovirus (hMPV), paarainfluenza virus (PIV) and respiratory syncytial virus (RSV). The antigens of the disclosed compositions are recombinant F protein polypeptides, which have been modified to stabilize the trimeric prefusion conformation. Nucleic acids encoding the antigens, as well as methods for their production and use are also provided.