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

VSEngineering 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

Engineering Contradiction:
Improveprotection against multiple pathogensVSAvoidprotection efficacy
Core Design Contradiction:
Adaptability or versatilityVSReliability

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.

Inventive Principle:
Principle #5Merging (Combining)

2Adaptability or versatility

If HVT vectors with multiple antigen inserts are constructed, then multivalent protection is achieved, but vector stability decreases

Engineering Contradiction:
Improveexpression of multiple antigensVSAvoidvector stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

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.

Inventive Principle:
Principle #1Segmentation

3Device complexity

If multiple antigens are expressed in a single HVT vector, then vaccine complexity is reduced, but manufacturing precision becomes more difficult

Engineering Contradiction:
Improvevaccine formulation complexityVSAvoidantigen expression control
Core Design Contradiction:
Device complexityVSManufacturing precision

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.

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS20250333766A1Recombinant HVT vectors expressing multiple antigens of avian pathogens and uses thereof
Publication Date: 2025.10.30 BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC
  • US20250333766A1 patent drawing
  • US20250333766A1 patent drawing
  • US20250333766A1 patent drawing

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.