VLPs Without M1 Matrix Protein for Broad Influenza Immunity
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Solution Overview
Problem
Current influenza vaccines face challenges in providing long-lasting immunity and are limited by the need for annual updates due to antigenic drift and shift, and they often lack proper conformational epitopes of HA and NA proteins, leading to inadequate protection against emerging viral strains.
Innovation Solution
Development of virus-like particles (VLPs) that express influenza membrane proteins such as HA, NA, or M2 without the M1 matrix protein, allowing for the creation of chimeric proteins with cytoplasmic or transmembrane domains fused with antigenic proteins from other strains or infectious agents, which self-assemble into structures that mimic the influenza virus but are non-infectious and can be easily purified.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional influenza vaccines are used, then they provide immunity against current strains, but they fail to provide long-lasting protection due to antigenic drift and shift
Solution Approach 1:
The patent creates virus-like particles (VLPs) that copy the structural and surface properties of influenza viruses without containing viral genetic material. These VLPs display conformational epitopes of HA and NA proteins that mimic the actual virus structure, enabling the immune system to recognize and respond to influenza viruses more effectively and durably.
Solution Approach 2:
The invention uses composite protein structures in the VLPs, combining HA and NA proteins in specific conformations that replicate the viral surface architecture. This composite approach allows the vaccine to present multiple antigenic features simultaneously, enhancing both the breadth and longevity of the immune response against diverse influenza strains.
2Manufacturing precision
If conventional vaccines are used, then they are easy to produce, but they lack proper conformational epitopes of HA and NA proteins
Solution Approach 1:
The patent extracts and isolates the critical conformational epitopes of HA and NA proteins from the complex viral structure. By separating these specific protein components and incorporating them into VLPs, the invention preserves the native three-dimensional structures and glycosylation patterns that are essential for immune recognition, while simplifying the production process.
Solution Approach 2:
The VLPs self-assemble in the cell culture system, automatically forming the correct three-dimensional structure and displaying the conformational epitopes in their native orientation. This self-assembly process eliminates the need for complex manual assembly steps and ensures consistent presentation of antigenic features, maintaining manufacturing precision while improving ease of production.
3Ease of manufacture
If virus-like particles without M1 matrix protein are produced, then they are easier to purify and non-infectious, but they must be engineered to self-assemble
Solution Approach 1:
The invention removes the M1 matrix protein from the VLP composition, which simplifies purification by eliminating the need to separate and inactivate this protein component. The VLPs can be isolated directly from cell culture supernatants through straightforward centrifugation and filtration steps, significantly easing the manufacturing process while maintaining their non-infectious nature.
Solution Approach 2:
The HA and NA proteins are engineered with specific interaction interfaces that enable them to self-assemble into VLPs without requiring the M1 matrix protein or other viral components. This self-assembly capability simplifies the expression system by eliminating the need to co-express multiple proteins, reducing the complexity of the protein expression system while maintaining structural integrity.
4Adaptability or versatility
If annual vaccine updates are required, then they address antigenic changes, but they create instability and require continuous development
Solution Approach 1:
The VLPs are designed to display universal conformational epitopes that are conserved across multiple influenza strains and subtypes. This universality allows a single vaccine formulation to provide broad protection against various influenza viruses, reducing the frequency of updates needed while maintaining adaptability to antigenic changes through the ability to swap protein subtypes.
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 VLPs induce protective immunity by displaying conformational epitopes that elicit neutralizing antibodies, offering broad-spectrum protection against multiple influenza strains and potential pandemic viruses, and can be updated to include new antigenic variants, providing a more stable and effective vaccine solution.
Implementation Method 1
allowing for the creation of chimeric proteins with cytoplasmic or transmembrane domains fused with antigenic proteins from other strains or infectious agents, which self-assemble into structures that mimic the influenza virus
Data Source
AI summary
The present invention discloses novel influenza virus-like particles (VLPs) that contain chimeric proteins or influenza membrane proteins. The chimeric proteins are derived from fragments of influenza membrane proteins fused to heterologous proteins. The invention includes antigenic formulations and vaccines comprising VLPs of the invention as well as methods of making and administering VLPs to vertebrates, including methods of inducing immunity to infections, such as influenza.