Chimeric Negative-Strand RNA Viruses for Multi-Pathogen Immunization
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Solution Overview
Problem
Current vaccine technologies face limitations in variability, particularly with chimeric vaccinia viruses, which lead to host resistance after multiple vaccinations, reducing their effectiveness in inducing immune stimulation, and negative-strand RNA viruses like influenza and Newcastle Disease Virus (NDV) offer genetic variability for broader vaccine formulations but require innovative approaches to enhance immune responses.
Innovation Solution
Engineering chimeric negative-strand RNA viruses to express fusion proteins that incorporate into their virions, combining the ectodomain of infectious agents with the transmembrane and cytoplasmic domains of influenza or NDV proteins, allowing for the induction of immune responses against multiple pathogens with a single virus administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chimeric vaccinia viruses are used for vaccination, then immune response is induced, but host resistance develops after multiple vaccinations reducing effectiveness
Solution Approach 1:
The patent changes the genetic parameters of the virus by using negative-strand RNA viruses with high genetic variability instead of DNA viruses. This allows continuous variation in viral epitopes, preventing host resistance development while maintaining immune stimulation effectiveness across multiple vaccinations.
Solution Approach 2:
The patent introduces dynamic genetic variability into the vaccine system by using negative-strand RNA viruses that naturally exhibit high mutation rates and genetic diversity. This dynamic variation in viral proteins ensures that the immune system continues to respond effectively without developing tolerance over time.
2Reliability
If multiple vaccinations are administered to maintain immune response, then immunity is sustained, but frequency of administration increases and cost rises
Solution Approach 1:
The patent creates chimeric viruses that can simultaneously present multiple antigenic determinants from different infectious agents. This multi-functionality allows a single vaccination to provide broad immune protection against multiple pathogens, reducing the need for repeated administrations and lowering overall vaccination costs.
Solution Approach 2:
The patent merges multiple antigenic functions into a single chimeric virus construct. By combining ectodomains from different infectious agents with the transmembrane and cytoplasmic domains of influenza or NDV proteins, the vaccine delivers multiple immune stimuli simultaneously, enhancing cost-effectiveness.
3Adaptability or versatility
If chimeric viruses express multiple foreign epitopes, then immune response against multiple pathogens is induced, but virus complexity increases
Solution Approach 1:
The patent segments the viral surface proteins by replacing only the ectodomain portions while retaining the transmembrane and cytoplasmic domains of the original influenza or NDV proteins. This segmentation strategy allows incorporation of multiple foreign epitopes while maintaining the structural integrity and functional simplicity of the viral envelope.
Data Source
AI summary
The present invention provides chimeric negative-stand RNA viruses that allow a subject, e.g., an avian, to be immunized against two infectious agents by using a single chimeric virus of the invention. In particular, the present invention provides chimeric influenza viruses engineered to express and incorporate into their virions a fusion protein comprising an ectodomain of a protein of an infectious agent and the transmembrane and cytoplasmic domain of an influenza virus protein. Such chimeric viruses induce an immune response against influenza virus and the infectious agent. The present invention also provides chimeric Newcastle Disease viruses (NDV) engineered to express and incorporate into their virions a fusion protein comprising the ectodomain of a protein of an infectious agent and the transmembrane and cytoplasmic domain of an NDV protein. Such chimeric viruses induce an immune response against NDV and the infectious agent.