Recombinant NDV Vectors Expressing IBV Ectodomain and GM-CSF

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Solution Overview

Problem

Current IBV vaccines face challenges due to the genetic diversity of the virus, leading to quick adaptation and increased virus fitness, and the expression of IBV spike proteins from different viral vectors has shown varying protection levels, with concerns about extending virus tropism when the S protein is expressed on the vector surface.

Innovation Solution

Development of recombinant Newcastle disease virus vectors expressing the infectious bronchitis virus (IBV) spike ectodomain and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are designed to induce an immune response without inserting the S protein into the viral envelope, thereby avoiding tropism concerns and enhancing protection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the complete IBV S protein is expressed on the surface of the virus vector, then immune response is enhanced, but the virus tropism may be extended causing safety concerns

Engineering Contradiction:

Improveprotection levelVSAvoidvirus tropism extension

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts only the ectodomain portion of the IBV S protein (amino acids 1-685) from the complete S protein structure. This extracted ectodomain retains the antigenic properties needed for immune response while removing the transmembrane and cytoplasmic domains that would enable incorporation into the viral envelope, thereby preventing tropism extension.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The S protein is segmented into distinct functional domains: the ectodomain (S1-S2 ectodomain) is separated from the transmembrane and cytoplasmic regions. This segmentation allows the antigenic ectodomain to be expressed independently without the harmful tropism-extending capabilities of the full protein.

Inventive Principle:

Principle #1Segmentation

2Reliability

If live vaccine viruses are used, then immunity is induced, but recombination events increase viral diversity and fitness

Engineering Contradiction:

Improveimmunity inductionVSAvoidviral diversity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses a Newcastle disease virus (NDV) vector as an intermediary carrier to deliver the IBV ectodomain antigen. This intermediary approach allows induction of immunity against IBV without using live IBV vaccine viruses, thereby preventing recombination events that would increase IBV diversity and fitness.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If the S ectodomain is expressed without multimerization, then production is simpler, but immune response is reduced

Engineering Contradiction:

Improveimmune responseVSAvoidprotein structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent creates a composite protein structure by fusing the IBV S ectodomain with a multimerization domain (such as Fc or IgG domains). This composite construction enables the ectodomain to form multimers, thereby enhancing immune response while maintaining relatively simple production procedures.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20240374711A1RECOMBINANT NEWCASTLE DISEASE VIRUS (rNDV) VECTORS AND METHODS OF USING THE SAME

Publication Date: 2024.11.14 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Disclosed are recombinant Newcastle disease virus (rNDV) vectors, related polynucleotides, and methods for eliciting an immune response against avian infectious bronchitis virus (IBV) or vaccinating against IBV.