Recombinant HVT Vectors for Multivalent Avian Influenza Vaccines
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Solution Overview
Problem
Current recombinant HVT vector strategies for developing multivalent vaccines against avian pathogens like AIV, MDV, IBDV, and NDV face challenges in predicting the success of antigen expression and stability, particularly when using multiple insertion sites or regulatory sequences like IRES or P2A.
Innovation Solution
The development of recombinant HVT vectors that insert heterologous polynucleotides encoding AIV H9-HA and additional avian antigens, such as IBDV or NDV, into the same non-essential site in the HVT vector genome, utilizing promoters like mCMV IE and sequences like IRES or P2A for expression regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple insertion sites are used in the HVT vector genome to express different antigens, then the vaccine can provide protection against multiple pathogens (multivalent), but the stability and expression success of the vector becomes unpredictable
Solution Approach 1:
The patent combines multiple antigen expression cassettes (AIV H9-HA and at least one additional avian pathogen antigen) into a single insertion site within the HVT vector genome. This merging approach consolidates multiple functions into one location, ensuring stable integration and predictable expression while maintaining multivalent protection capability.
2Adaptability or versatility
If multiple insertion sites are used in the HVT vector genome, then multiple antigens can be expressed, but the device complexity increases making success prediction difficult
Solution Approach 1:
The patent merges multiple antigen expression functions into a single insertion site by using a polycistronic expression cassette containing multiple open reading frames (ORFs) separated by IRES or P2A sequences. This reduces the number of insertion sites needed from multiple to one, thereby simplifying the overall recombinant strategy while maintaining the ability to express multiple antigens.
3Device complexity
If regulatory sequences like IRES or P2A are used to express multiple antigens from a single insertion site, then the device complexity is reduced, but the stability and expression success becomes unpredictable
Solution Approach 1:
The patent employs universal regulatory elements (CMV immediate early promoter and IRES or P2A sequences) that have been proven to function reliably across different antigen expression contexts. These universal components ensure consistent and stable expression of multiple different antigens from a single insertion site, making the system predictable and reliable.
4Reliability
If a single insertion site is used to express multiple antigens, then the vector stability is improved, but the vaccine can only provide protection against limited pathogens
Solution Approach 1:
The patent implements a nested structure where multiple antigen-encoding open reading frames (ORFs) are nested within a single expression cassette, which itself is inserted into the HVT vector genome. This nested organization allows multiple pathogens to be covered within a single stable integration site, achieving both vector stability and broad pathogen protection.
Data Source
AI summary
The present invention provides recombinant herpes virus of turkeys (HVT) viral vectors comprising a heterologous polynucleotide encoding an avian influenza antigen. The recombinant viral vectors are suitable for use in immunogenic compositions and vaccines, and can provide protection against avian influenza and other pathogens when administered to an avian.