Multi-Antigen Chimeric Monkeypox Vaccine for IMV and EEV Protection
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Solution Overview
Problem
Current poxvirus vaccines, particularly those for monkeypox, face challenges such as incomplete attenuation, complex components leading to side effects, low immunogenicity, and potential immunosuppression, with existing live virus vaccines posing safety risks and uncertain efficacy due to mutation and unsuitable for all populations.
Innovation Solution
A multi-immunogen chimeric or mixed poxvirus antigen comprising specific monkeypox virus proteins A35R, M1R, and B6R, designed to elicit a targeted immune response, with a single-chain polypeptide or mixed formulation, and a method for production using mammalian, insect, yeast, or bacterial cells, encapsulated in lipid nanoparticles for vaccines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If live virus vaccines are used to prevent monkeypox virus infection, then the vaccines retain complete viral antigens, but there is the possibility of incomplete attenuation or restoration of virulence after mutation
Solution Approach 1:
The patent extracts only the essential immunogenic components (A35R, M1R, and B6R proteins) from the complete virus, creating a recombinant protein vaccine that eliminates unnecessary viral components while retaining protective antigens. This extraction approach maintains immunogenicity while improving safety by removing potential sources of virulence restoration.
Solution Approach 2:
The vaccine divides the viral antigen portfolio into distinct functional segments: A35R for IMV neutralization, B6R for EEV neutralization, and M1R for intracellular antigen presentation. This segmentation allows precise control over which viral components are included, eliminating the need for complete viral antigen retention while maintaining protective immunity.
2Quantity of substance
If live virus vaccines contain all viral antigens, then they have complex components, but this increases the possibility of causing side effects
Solution Approach 1:
The patent extracts only the three essential immunogenic proteins (A35R, M1R, B6R) from the complete virus, eliminating complex and potentially harmful viral components while retaining the core protective antigens. This reduces side effects by removing unnecessary viral elements.
Solution Approach 2:
The vaccine segments the antigen composition into three distinct protective proteins, each targeting specific viral structures or immune pathways. This segmentation eliminates redundant viral components that could cause side effects while maintaining comprehensive immune coverage.
3Quantity of substance
If live virus vaccines contain all viral components, then the proportion of effective immunogenic components is relatively low, but this results in weak immunogenicity even at the same dose of vaccination
Solution Approach 1:
The patent extracts and concentrates only the three most effective immunogenic proteins (A35R, M1R, B6R) that directly neutralize viral particles or stimulate protective immune responses. This extraction increases the proportion of effective components from a small fraction to 100% of the vaccine composition, thereby enhancing immunogenicity.
Solution Approach 2:
The vaccine segments the antigen composition to focus exclusively on the three proteins with demonstrated protective efficacy. This segmentation eliminates dilution by non-immunogenic or less effective viral components, concentrating the immunogenic payload to maximize immune response at lower doses.
4Quantity of substance
If live virus vaccines include some viral components, then these components may inhibit host immunity, but this has a counterproductive effect and reduces the immunogenicity of the vaccine
Solution Approach 1:
The patent extracts and excludes viral components known to have immunosuppressive functions while retaining the protective antigens. By taking out only the essential immunogenic proteins and omitting immunosuppressive viral elements, the vaccine eliminates the counterproductive effect while maintaining immunogenicity.
Solution Approach 2:
The vaccine segments the viral antigen portfolio to exclude components with immunosuppressive properties. By selectively including only A35R, M1R, and B6R proteins and omitting other viral components that may inhibit host immunity, the vaccine achieves pure immunogenicity without counteracting suppressive effects.
Data Source
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AI summary
The present application relates to a multi-immunogen chimeric or mixed antigen for a poxvirus, particularly monkeypox virus, related products, and preparation method and use thereof. The chimeric or mixed antigen of the present application comprises three immunogens: (1) a monkeypox virus A35R protein or an antigenic fragment thereof (or a peptide fragment derived therefrom), (2) a monkeypox virus M1R protein or an antigenic fragment thereof (or a peptide fragment derived therefrom), and (3) a monkeypox virus B6R protein or an antigenic fragment thereof (or a peptide fragment derived therefrom), and can elicit an immune response against two types of infectious virus particles, namely intracellular mature virus particles (IMV) and extracellular envelope virus particles (EEV), thereby efficiently inducing specific immunoprotective effects against the monkeypox virus. Moreover, the poxvirus vaccine of the present application features good safety, rapid response, and scalable production capacity, thus showing excellent clinical application prospects.