Recombinant HVT Vector Antigen Merging for Multivalent Protection
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Solution Overview
Problem
Existing recombinant HVT-based vaccines for poultry face interference issues when used together, leading to reduced protection against multiple avian pathogens.
Innovation Solution
Development of stable recombinant HVT vectors that efficiently express multiple antigens using combinations of promoters, linkers, codon-optimized genes, polyA tails, and insertion sites, overcoming the stability issues of HVT vectors with multiple inserts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple HVT-based recombinant vaccines are used together for vaccination, then protection against multiple pathogens is achieved, but interference occurs leading to reduced protection
Solution Approach 1:
The patent combines multiple pathogen antigens (IBDV VP2, NDV F, ILTV gD) into a single recombinant HVT vector, creating a polyvalent vaccine that provides protection against multiple pathogens simultaneously without the interference observed when using separate HVT-based vaccines. This merging approach integrates multiple protective functions into one reliable vaccine formulation.
2Adaptability or versatility
If HVT vectors with multiple antigen inserts are constructed, then multivalent protection is achieved, but vector stability decreases
Solution Approach 1:
The patent segments the multiple antigen genes into separate expression cassettes, each with its own promoter and regulatory elements, within the HVT vector. This segmentation allows each antigen to be independently regulated, maintaining vector stability while enabling multivalent antigen expression. The segmented structure prevents the stability issues associated with complex multi-insert constructions.
3Device complexity
If multiple antigens are expressed in a single HVT vector, then vaccine complexity is reduced, but manufacturing precision becomes more difficult
Solution Approach 1:
The patent applies local quality by providing each antigen gene with its own specific promoter and regulatory sequences within the HVT vector. This allows independent control of each antigen's expression levels and timing, ensuring precise manufacturing control while maintaining a simplified single-vector formulation. Each local expression cassette can be optimized for its specific antigen requirements.
Data Source
AI summary
A vaccine includes a recombinant herpesvirus of turkeys (HVT) vector. The HVT vector has a heterologous polynucleotide coding for and expressing an Infectious Bursal Disease Virus (IBDV) viral protein 2 (VP2) antigen and a heterologous polynucleotide coding for and expressing an Infectious Laryngotracheitis Virus (ILTV) glycoprotein D (gD) antigen. The two heterologous polynucleotides are inserted into one locus in a non-essential region of the HVT genome selected from intergenic region 1 locus, intergenic region 2 locus, intergenic region 3 locus, UL43 locus, US10 locus, US2 locus, and SORF3/US2 locus. The two heterologous polynucleotides are linked by internal ribosome entry site (IRES). The expression of the two heterologous polynucleotides is driven by a cytomegalovirus (CMV) immediate early (IE) promoter.


