Hepatitis A Virus Production in Vero Cells With Fewer Subcultures

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Solution Overview

Problem

Existing methods for producing hepatitis A virus are slow and inefficient, requiring numerous subcultures and using endangered cell lines, leading to supply shortages and demand instability in vaccines.

Innovation Solution

A method involving a hepatitis A virus gene with specific mutations (SEQ ID NO: 1) and an expression cassette is used to rapidly and stably produce the virus by reducing subculturing steps to 6 times, utilizing safe and approved cell lines like MA104 and Vero cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional cell lines (AGMK, FRhK-4, BS-C-1) are used for hepatitis A virus amplification, then virus production is achieved, but the process requires numerous subcultures (50 times) and uses endangered species cells, leading to long production time and supply instability

Engineering Contradiction:

Improvevirus production efficiencyVSAvoidproduction time

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

The patent changes the cell line parameter from traditional endangered species cells (AGMK, FRhK-4, BS-C-1) to safe, approved cell lines (MA104, Vero). This parameter change enables reduced subculturing steps from 50 times to 6 times while maintaining virus production capability, thereby shortening production time and improving efficiency without compromising safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a simplified copy of the virus amplification process by using recombinant DNA technology with expression cassettes containing hepatitis A virus genes. This copying approach allows the virus to be produced through fewer subcultures (6 times) compared to traditional methods (50 times), significantly reducing production time while maintaining viral yield

Inventive Principle:

Principle #26Copying

2Productivity

If traditional cell lines are used, then virus amplification is possible, but the cell lines are derived from endangered species (Cercopithecidae family) restricted by CITES, making import difficult into Korea

Engineering Contradiction:

Improvevirus amplification capabilityVSAvoidcell line availability

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent replaces expensive, restricted endangered species cell lines with safe, approved, and readily available cell lines (MA104, Vero). These alternative cell lines are not subject to CITES restrictions, making them easy to obtain and manufacture with, while maintaining the capability for effective virus amplification

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent introduces recombinant DNA technology as an intermediary method between the hepatitis A virus and host cells. By using expression cassettes with viral genes inserted into safe cell lines, the system acts as a mediator that enables virus production without requiring direct use of endangered species cells, thus resolving the availability issue

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If numerous subcultures (50 times) are performed to adapt virus to cell lines, then virus production is optimized, but the process becomes cumbersome and time-consuming

Engineering Contradiction:

Improvevirus adaptation to cell lineVSAvoidsubculturing process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by pre-adapting the hepatitis A virus to the new cell lines (MA104, Vero) through a reduced number of subcultures (6 times) before actual virus production. This preliminary adaptation step, combined with the use of expression cassettes containing viral genes, significantly reduces the total subculturing steps from 50 times to 6 times, making the process less complex while maintaining viral adaptability and production reliability

Inventive Principle:

Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The method significantly reduces production time from months to 4-5 months, ensuring stable and high-yield virus production suitable for vaccine manufacturing, addressing supply issues and enabling consistent vaccine availability.

Implementation Method 1

transfecting the host cell with a vector inserted with an expression cassette comprising a hepatitis A virus gene

Methodology Applied

Scientific EffectTransfection:

Implementation Method 2

infecting the host cell with a virus obtained by transfecting the host cell with a vector inserted with an expression cassette comprising a hepatitis A virus gene for preparing the hepatitis A virus, and subculturing the same

Methodology Applied

Scientific EffectViral replication:

Data Source

PatentUS12558417B2Hepatitis A virus preparation method and hepatitis A virus prepared according to method

Publication Date: 2026.02.24 SK BIOSCI CO LTD

AI summary

The present invention relates to a hepatitis A virus production method and hepatitis A virus produced according to the method, and, more specifically, to: a hepatitis A virus production method and hepatitis A virus produced according to the method, the method comprising the step of infecting a host cell with a virus obtained by transforming a host cell with a vector comprising an expression cassette, which comprises a hepatitis A virus gene, for hepatitis A virus preparation, and subculturing same.