Multivalent Recombinant HVT Vectors for Stable Antigen Expression

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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 stability issues and interference.

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 avian pathogens is achieved, but interference occurs leading to reduced protection levels

Engineering Contradiction:

Improveprotection against multiple avian pathogensVSAvoidprotection level

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent combines multiple pathogen antigen genes (NDV F gene, IBDV VP2 gene, ILTV gD gene) into a single HVT vector genome, creating a multivalent vaccine that provides protection against multiple avian pathogens simultaneously without the interference issues observed when using separate HVT-based vaccines

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The HVT vector is engineered to express multiple different antigens from various avian pathogens (Newcastle disease virus, Infectious bursal disease virus, Infectious laryngotracheitis virus) within a single vaccine formulation, making it a universal platform for multi-pathogen protection

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If multiple heterologous polynucleotides are inserted into HVT vector, then multiple antigens are expressed, but stability of the vector decreases

Engineering Contradiction:

Improveexpression of multiple antigensVSAvoidvector stability

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent divides the multiple antigen genes into separate expression cassettes, each with its own promoter and regulatory elements, inserted at specific locations (IG1 and IG2) in the HVT genome. This segmentation allows each gene to be independently regulated and maintained, improving overall vector stability while expressing multiple antigens

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different promoters (CMV immediate early promoter, SV40 promoter) and regulatory sequences are used for different antigen genes based on their specific expression requirements. This local optimization of regulatory elements ensures stable and appropriate expression levels for each antigen without compromising overall vector stability

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS12385068B2Recombinant HVT vectors expressing multiple antigens of avian pathogens and uses thereof

Publication Date: 2025.08.12 BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC

AI summary

The present invention provides recombinant herpesvirus of turkeys (HVT) vectors that contain and express antigens of avian pathogens, compositions comprising the recombinant HVT vectors and polyvalent vaccines comprising the recombinant HVT vectors. The present invention further provides methods of vaccination against a variety of avian pathogens and method of producing the recombinant HVT vectors.