Multi-Immunogen mRNA Vaccine Composition for Safer Monkeypox Immunity
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Solution Overview
Problem
Current vaccines for monkeypox virus, such as JYNNEOS™ and ACAM2000®, face challenges including potential mutation, safety risks, complex components leading to side effects, low immunogenicity, and uncertainty in immune efficacy due to incomplete attenuation or inhibition of host immunity, especially for poxviruses like monkeypox virus.
Innovation Solution
A polynucleotide encoding a multi-immunogen chimeric or mixed poxvirus antigen comprising monkeypox virus A35R and MIR proteins or their antigenic fragments, used to develop a nucleic acid vaccine that specifically targets and elicits immune responses against monkeypox virus.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If attenuated live virus vaccines are used to retain all viral antigens, then comprehensive immune coverage is achieved, but safety risks increase due to potential incomplete attenuation or mutation
Solution Approach 1:
The patent extracts only the essential immunogenic components (A35R and MIR proteins) from the complete viral antigen suite. This selective extraction eliminates harmful viral components while preserving protective immunity, directly resolving the contradiction between comprehensive coverage and safety.
Solution Approach 2:
The vaccine divides the viral antigen into discrete functional segments (A35R protein and MIR protein) rather than using the complete viral antigen complex. This segmentation allows selective inclusion of only those components necessary for immunity, eliminating harmful elements and resolving the safety-coverage contradiction.
2Reliability
If all viral components are included in the vaccine, then complete antigenic representation is achieved, but vaccine complexity and side effects increase
Solution Approach 1:
The invention extracts and includes only the two most critical immunogenic proteins (A35R and MIR) needed for protective immunity, eliminating unnecessary viral components. This reduces vaccine complexity and minimizes side effects while preserving complete antigenic representation of essential targets.
Solution Approach 2:
The patent changes the composition parameter of the vaccine from containing all viral antigens to containing only specific immunogenic proteins. This parameter optimization achieves complete representation of protective antigens while reducing overall complexity and harmful components.
3Reliability
If live virus vaccines are used to ensure viral replication, then immune response is enhanced, but risks of encephalitis, myocarditis, and progressive vaccinia increase
Solution Approach 1:
The patent uses mRNA as a temporary, non-replicating delivery vehicle that degrades after delivering its genetic instructions. This disposable approach provides sufficient immune stimulation without the persistent replication risks of live virus vaccines, enhancing immune response while eliminating serious safety risks.
Solution Approach 2:
The invention introduces mRNA as an intermediary that carries viral antigen information without containing the actual virus. This mediator enables immune system training with viral antigens while preventing the replication and transmission risks associated with live virus vaccines.
4Object-affected harmful factors
If conventional vaccines are used that cannot be replicated in the human body, then safety is improved, but immune efficacy is moderately reduced
Solution Approach 1:
The patent optimizes the mRNA vaccine parameters including codon optimization, 5' cap structure, and 3' poly-A tail to enhance translation efficiency and immune recognition. These parameter changes enable non-replicating mRNA to achieve immune efficacy comparable to or exceeding traditional vaccines while maintaining superior safety.
Solution Approach 2:
The invention uses composite lipid nanoparticle formulations to deliver mRNA, combining multiple functional components (ionizable lipids, PEGylated lipids, cholesterol, phospholipids) to enhance stability, cellular uptake, and immune activation. This composite approach compensates for the non-replicating nature of mRNA while maintaining safety.
Data Source
AI summary
Provided are a polynucleotide encoding a chimeric or mixed antigen of poxvirus multiple immunogens, a related nucleic acid product thereof, and the use thereof in the preparation of a vaccine for preventing and/or treating poxvirus (in particular monkeypox virus) infection. The chimeric or mixed antigen of the poxvirus multiple immunogens encoded by the polynucleotide comprises two immunogens: a monkeypox virus A35R protein or an antigenic fragment thereof (or an appropriate variant thereof) and a monkeypox virus MIR protein or an antigenic fragment thereof (or an appropriate variant thereof). The immunogen components of the chimeric or mixed nucleic acid vaccine based on the polynucleotide are clear, and the chimeric or mixed nucleic acid vaccine can efficiently stimulate specific immune responses (for example, generating a protective antibody) against poxvirus (in particular monkeypox virus), can be used for preventing and/or treating poxvirus (in particular monkeypox virus), and has high clinical application prospects.