Modified HA Trimer Interface for Influenza Cell Culture Growth

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Solution Overview

Problem

Certain influenza viruses are less amenable to growth and replication in cell culture, such as Madin Darby Canine Kidney (MDCK) cells, posing challenges in vaccine manufacture.

Innovation Solution

Modifying specific amino acid residues in the trimer interface region of the HA protein, particularly for H2 subtype, to enhance stability and facilitate growth in cell culture.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional influenza viruses are used for vaccine production in cell culture, then the vaccine manufacturing process can be simplified, but certain influenza viruses show poor growth and replication in cell culture conditions

Engineering Contradiction:

Improveease of vaccine manufactureVSAvoidvirus yield in cell culture

Core Design Contradiction:

Ease of manufactureVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying specific amino acid residues in the HA protein sequence. The modification changes the physical-chemical properties of the HA protein, specifically enhancing its stability and ability to support viral replication in cell culture conditions, thereby resolving the contradiction between ease of manufacture and virus yield

Inventive Principle:

Principle #35Parameter changes

2Productivity

If amino acid modifications are introduced to improve virus growth in cell culture, then virus yield and stability are enhanced, but the HA protein structure is altered

Engineering Contradiction:

Improvevirus yieldVSAvoidHA protein structure stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies local quality by introducing modifications at specific localized positions (amino acid residues 380-460) in the HA protein rather than throughout the entire structure. This localized modification approach enhances virus yield and stability in cell culture while preserving the overall structural integrity and functional properties of the HA protein

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20260071191A1Modified influenza viruses

Publication Date: 2026.03.12 SEQIRUS INC

AI summary

The present disclosure relates to the field of modified viruses and viral proteins. More particularly, this disclosure relates to modified haemagglutinin proteins, influenza viruses expressing such proteins and methods of making same