Recombinant Avian Herpes Viruses With Stable Multivalent Expression
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Solution Overview
Problem
Existing multivalent recombinant herpes viruses for avian diseases are unstable, leading to deletion of foreign genes during repeated passaging in culture cells, making them ineffective as vaccines.
Innovation Solution
Insertion of foreign antigen genes into specific non-coding regions of the herpes virus genome, such as between UL44 and UL45, UL45 and UL46, US10 and SORF3, and SORF3 and US2, using distinct promoters like chicken beta-actin, Murine Cytomegalovirus, and Simian virus, ensures stable co-expression of multiple antigens in avian cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple foreign antigen genes are inserted into recombinant herpes viruses, then the vaccine can provide simultaneous immunity against multiple avian diseases, but the virus becomes unstable and foreign genes are deleted during repeated passaging
Solution Approach 1:
The patent divides the herpes virus genome into multiple distinct non-coding regions (UL44-UL45, UL45-UL46, US10-SORF3, SORF3-US2) and inserts different foreign antigen genes into separate regions. This segmentation allows each antigen gene to be independently stabilized in its own genomic compartment, preventing mutual interference and deletion during viral passaging while maintaining multivalent immunity capability
Solution Approach 2:
The patent applies different promoters (chicken beta-actin, Murine Cytomegalovirus, Simian virus promoters) to different inserted antigen genes based on their specific insertion locations. This local quality approach optimizes the expression stability and efficiency of each antigen gene in its specific genomic context, ensuring stable co-expression of multiple antigens without compromising viral genome stability
2Duration of action of stationary object
If foreign genes are inserted into the herpes virus genome, then the duration of immunity is increased through persistent infection, but the insertion sites may cause gene deletion during culture cell passaging
Solution Approach 1:
The patent performs preliminary selection and characterization of four specific non-coding regions in the herpes virus genome before inserting foreign antigen genes. These regions were pre-validated to ensure they maintain genomic stability during repeated passaging. By conducting this preliminary action, the patent ensures that the inserted genes remain stable and reliably expressed throughout the persistent infection period, maintaining both long-duration immunity and gene expression reliability
3Adaptability or versatility
If multiple recombinant herpes viruses are administered to achieve broad disease coverage, then immunity against multiple diseases is achieved, but competition and immunosuppression between pathogens occur
Solution Approach 1:
The patent merges multiple foreign antigen genes into a single recombinant herpes virus vector, creating a multivalent vaccine that provides immunity against multiple diseases simultaneously. This merging approach eliminates the need to administer multiple separate viral vectors, thereby avoiding competition and immunosuppression between different pathogens while maintaining broad disease coverage through co-expression of multiple antigens from the same stable virus
Data Source
AI summary
The present invention relates to a recombinant avian herpes virus, which comprises at least two recombinant nucleotide sequences, each recombinant nucleotide sequence encoding a distinct antigenic peptide, wherein the at least two recombinant nucleotide sequences are inserted into distinct non-coding regions of the viral genome chosen among the region located between UL44 and UL45, the region located between UL45 and UL46, the region located between US10 and SORF3, and the region located between SORF3 and US2.