Influenza B Virus Composition for High-Titer Vaccine Replication
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Solution Overview
Problem
Existing influenza B virus vaccines face challenges in efficiently producing high yields in cultured cells and embryonated chicken eggs, leading to suboptimal vaccine production efficiency and cost-effectiveness.
Innovation Solution
Introduction of specific mutations in the 'internal' genes and viral glycoproteins HA and NA of influenza B viruses, enhancing viral titers and HA yields through the use of reassortant or recombinant viruses with optimized growth-enhancing residues in polypeptides and non-coding nucleotide sequences, allowing for higher replication in cell culture and eggs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional influenza B virus strains are used for vaccine production, then the production process is simple, but the viral titers and HA yields are insufficient
Solution Approach 1:
The patent applies parameter changes by introducing specific mutations in the 'internal' genes and viral glycoproteins HA and NA of influenza B viruses. These genetic parameter modifications enhance viral replication efficiency and HA production, achieving significantly higher viral titers (up to 10³ PFU/mL in cultured cells and 10⁷ EID50/mL in eggs) without fundamentally changing the vaccine production process architecture.
Solution Approach 2:
The patent implements local quality by making targeted modifications to specific regions of the viral genome. Rather than altering the entire virus, specific mutations are introduced in internal genes and glycoprotein sequences that locally enhance replication and antigen production capabilities, while maintaining the overall viral structure and safety profile.
2Productivity
If wild-type influenza B viruses are used, then the virus structure is stable, but the replication efficiency in cell culture and eggs is low
Solution Approach 1:
The patent changes viral parameters by introducing specific mutations in internal genes and surface glycoproteins that enhance replication efficiency. These controlled parameter modifications improve productivity in cell culture and embryonated eggs while maintaining virus strain stability through careful selection of mutations that preserve essential viral functions and antigenic properties.
Solution Approach 2:
The patent creates reassortant or recombinant virus copies that incorporate beneficial mutations from different parental strains. By copying and combining specific genetic elements that enhance replication and HA production, the patent achieves improved productivity while maintaining the stability of essential viral components through selective reassortment or recombination.
3Quantity of substance
If conventional influenza B virus strains are used, then the manufacturing process is straightforward, but the cost-effectiveness is suboptimal
Solution Approach 1:
The patent modifies viral parameters by introducing specific mutations that enhance HA production efficiency. These genetic modifications lead to significantly higher HA yields per unit volume of culture, improving the quantity of antigen available for vaccine formulation. The manufacturing process remains relatively straightforward as the modifications are incorporated into the virus itself rather than requiring complex external production steps.
Data Source
AI summary
The invention provides a composition useful to prepare high titer influenza B viruses, e.g., in the absence of helper virus, which includes internal genes from an influenza B virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, that confer enhanced growth in cells in culture, such as MDCK cells, or in eggs.