Multi-Antigen mRNA Vaccine to Avoid FIPV ADE
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Solution Overview
Problem
Current FIPV vaccines fail to provide effective protection due to antibody-dependent enhancement (ADE) and lack of satisfactory cell-mediated immunity, leading to nearly all infections resulting in cat deaths.
Innovation Solution
A multi-antigen mRNA vaccine formulation encoding M, N, S, S_ec, or SII proteins of FIPV, designed to stimulate cell-mediated immune responses, with adaptively modified proteins to reduce virulence while maintaining immunogenicity, and optionally including signal peptides and MITD sequences to enhance immune stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If humoral immunity-based vaccines are used against FIPV, then antibody production is enhanced, but antibody-dependent enhancement (ADE) occurs leading to worsened infection outcomes
Solution Approach 1:
The patent extracts and eliminates the harmful ADE effect by shifting from humoral immunity (antibody-based) to cell-mediated immunity (T cell-based) vaccination approach. The mRNA vaccine is specifically designed to target intracellular antigens that stimulate T cell responses rather than antibody production, thereby removing the source of ADE while maintaining protective immunity.
Solution Approach 2:
The patent changes the immune response parameter from humoral (antibody-mediated) to cell-mediated (T cell-mediated) immunity. This fundamental parameter change transforms the mechanism of protection from extracellular neutralization to intracellular recognition and destruction of infected cells, avoiding ADE while providing effective protection against FIPV.
2Quantity of substance
If conventional FIPV vaccines are used, then immune response is stimulated, but cell-mediated immunity remains insufficient leading to vaccine failure
Solution Approach 1:
The patent substitutes the conventional vaccine mechanism (which relies on humoral immunity) with an mRNA-based mechanism that directly delivers genetic instructions for intracellular antigen production. This substitution enables endogenous antigen expression within host cells, which is essential for stimulating robust cell-mediated immunity through MHC class I presentation to CD8+ T cells.
Solution Approach 2:
The patent introduces mRNA as an intermediary carrier that delivers viral antigen sequences into host cells. This mRNA intermediary enables the host's own cellular machinery to produce viral antigens internally, creating a more effective stimulus for T cell activation compared to external protein administration, thereby enhancing cell-mediated immune responses.
3Reliability
If multi-antigen mRNA vaccine is administered, then cell-mediated immunity is enhanced, but vaccine complexity increases
Solution Approach 1:
The patent merges multiple viral antigen sequences (S protein, N protein, M protein) into a single mRNA vaccine formulation. This consolidation allows simultaneous presentation of multiple antigens to the immune system through a single administration vehicle, enhancing cell-mediated immunity against multiple viral components while managing complexity through unified delivery.
Solution Approach 2:
The patent creates a multi-functional mRNA vaccine that simultaneously targets multiple viral proteins (S, N, M) and stimulates multiple arms of the immune system. The single mRNA formulation serves multiple functions: encoding multiple antigens, enabling intracellular expression, and stimulating T cell responses against various viral components, thereby providing broad protection through a unified platform.
Data Source
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AI summary
Provided is a pharmaceutical formulation. The pharmaceutical formulation includes a nucleic acid fragment. The nucleic acid fragment is mRNA and includes at least one of a first nucleic acid fragment, a second nucleic acid fragment, or a third nucleic acid fragment. The first nucleic acid fragment encodes an M protein of feline infectious peritonitis virus; the second nucleic acid fragment encodes an N protein of feline infectious peritonitis virus; the third nucleic acid fragment encodes an S protein, an S_ec protein, or an SII protein of feline infectious peritonitis virus; and the first nucleic acid fragment, the second nucleic acid fragment, and the third nucleic acid fragment are linked or not linked.