Duck Embryonic Stem Cell Lines for Retrovirus-Free Vaccine Production

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Solution Overview

Problem

Current viral vaccine production technologies using embryonated chicken eggs and primary chicken embryo fibroblasts are hindered by contamination risks, resource inefficiencies, and regulatory concerns due to the presence of avian endogenous retroviruses, leading to the need for safer, more efficient, and scalable production methods.

Innovation Solution

Development of continuous diploid avian cell lines derived from embryonic stem cells of ducks and chickens that are free of replication-competent endogenous retrovirus particles, allowing for the efficient production of viral vaccines without contamination risks and regulatory hurdles, using a process that involves isolating embryonic stem cells and gradually transitioning them to grow in serum-free media without exogenous growth factors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If embryonated chicken eggs and primary chicken embryo fibroblasts are used for viral vaccine production, then vaccine production is achieved, but contamination with avian endogenous retroviruses occurs

Engineering Contradiction:
Improvevaccine safetyVSAvoidretrovirus contamination
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and eliminates the harmful retroviral elements from the avian cell substrate by using cell lines specifically selected and engineered to be free of replication-competent endogenous retroviruses, while retaining the useful properties for virus production

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the use of live embryonated eggs and primary embryo fibroblasts with established cell lines that can be maintained and used repeatedly, eliminating the need for continuous sourcing of new embryonic materials and reducing contamination risks

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Productivity

If embryonated chicken eggs are used for viral vaccine production, then vaccine manufacturing is achieved, but resource inefficiency and high costs occur

Engineering Contradiction:
Improvevaccine production efficiencyVSAvoidresource consumption
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The invention establishes continuous cell lines that can be maintained indefinitely in culture, allowing continuous production of vaccine viruses without the intermittent need to source new embryonated eggs, thereby improving productivity and reducing resource waste

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The invention performs preliminary establishment and characterization of retrovirus-free cell lines before vaccine production, creating a ready-to-use substrate that eliminates the need for repeated sourcing and processing of embryonic materials

Inventive Principle:
Principle #10Preliminary action

3Ease of manufacture

If avian cell substrates containing endogenous retroviruses are used, then viral vaccine production is achieved, but regulatory compliance becomes difficult

Engineering Contradiction:
Improveproduction feasibilityVSAvoidregulatory compliance
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The invention removes the regulatory obstacle by extracting and eliminating replication-competent endogenous retroviruses from the avian cell substrate, creating a compliant production system that maintains manufacturing feasibility

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentUS9822345B2Method of making a virus using duck embryonic derived stem cell lines
Publication Date: 2017.11.21 VALNEVA
  • US9822345B2 patent drawing
  • US9822345B2 patent drawing
  • US9822345B2 patent drawing

AI summary

The present invention relates to the development and manufacturing of viral vaccines. In particular, the invention relates to the field of industrial production of viral vectors and vaccines, more in particular to the use of avian embryonic stem cells, preferably the EBx® cell line derived from duck embryonic stem cells, for the production of viral vectors and viruses. The invention is particularly useful for the industrial production of viral vaccines to prevent viral infection of humans and animals.