Bordetella Fermentation Medium Conditioning for Higher PT Yield
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Solution Overview
Problem
Bordetella species, particularly Bordetella pertussis and Bordetella parapertussis, are difficult to grow in high concentrations and express virulence factors like pertussis toxin (PT) efficiently, posing challenges for large-scale vaccine production.
Innovation Solution
A medium conditioning step involving temperature control and oxygen volumetric mass transfer coefficient (kLa) manipulation is applied to sterile growth medium before inoculation, enhancing Bordetella fermentation performance by increasing PT yield, biomass, and reducing fermentation time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Bordetella species are cultivated in conventional growth medium, then fermentation can proceed, but PT yield is low and biomass is insufficient
Solution Approach 1:
The growth medium is conditioned prior to inoculation through aeration and temperature control (28-35°C for 20-35 hours) to pre-equilibrate the medium, ensuring optimal conditions are ready before Bordetella cells are introduced. This preliminary preparation significantly enhances subsequent PT production and biomass accumulation.
Solution Approach 2:
The invention modifies physical parameters of the growth medium by controlling temperature (28-35°C) and oxygen transfer coefficient (kLa of 10-130 h⁻1) during the conditioning phase. These parameter adjustments create favorable conditions for Bordetella metabolism, leading to increased PT yield and reduced fermentation time.
2Productivity
If Bordetella species are grown in conventional medium, then culture can be maintained, but fermentation time is extended
Solution Approach 1:
The medium is pre-conditioned through aeration and temperature control before inoculation, preparing the environment to support rapid Bordetella growth and metabolism from the start. This eliminates delays in establishing optimal growth conditions during the fermentation process.
Solution Approach 2:
By optimizing temperature (28-35°C) and oxygen availability (kLa of 10-130 h⁻1) during the conditioning phase, the medium is prepared to support high metabolic rates and rapid cell division, thereby reducing the overall fermentation time required to achieve target PT production.
3Quantity of substance
If Bordetella virulence factors are expressed in conventional medium, then production can occur, but expression efficiency is low
Solution Approach 1:
The growth medium is conditioned beforehand through controlled aeration and temperature maintenance to pre-establish optimal metabolic conditions. This ensures that when Bordetella cells are inoculated, they immediately begin efficient virulence factor production without delay.
Solution Approach 2:
The invention optimizes physical parameters including temperature (28-35°C) and oxygen transfer coefficient (kLa of 10-130 h⁻1) during medium conditioning. These parameter adjustments create an environment that maximizes Bordetella metabolic activity and virulence factor synthesis efficiency.
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 process results in at least 10% higher PT yield and biomass, with fermentation time reduced by at least 10%, producing a sterile conditioned growth medium suitable for efficient Bordetella protein production.
Implementation Method 1
holding the growth medium at a temperature between about 28° C. and about 35° C. for about 20 to 35 hours
Implementation Method 2
stirring and/or aerating the growth medium to produce an oxygen volumetric mass transfer coefficient (kLa) of about 10 h−1 to about 130 h−1
Implementation Method 3
Bordetella species are fastidious organisms which are difficult to grow in high concentrations, furthermore it is difficult to express Bordetella virulence factors
Data Source
AI summary
The present invention relates to processes for Bordetella fermentation and virulence factor production, especially PT production, for large scale manufacturing. More particularly, processes including a medium conditioning step carried out prior to inoculation.