Gene-expression-based quality scores indicate optimal harvest point in Bordetella pertussis cultivation for vaccine production.

The evolution of vaccine product quality during batch cultivation of Bordetella pertussis, the causative agent of whooping cough, was investigated with the goal to determine the optimal harvest point. The process was explored by measuring mRNA expression at frequent intervals during cultivation. The genes that are involved in virulence are already known for this product and changes in their expression levels are proposed to be indicative for product quality.

Improving the cellular pertussis vaccine: increased potency and consistency.

Although Europe, Canada and the US have switched from cellular to acellular pertussis vaccines, most developing countries will continue to use the more cost effective cellular vaccine. Consistency of production however is the typical problem inherent to cellular vaccines. Optimising the production process of cellular pertussis bulk suspensions using product potency as a measure is not possible, since the mandatory animal test to measure potency has little discriminatory power.

Fed-batch cultivation of Bordetella pertussis: metabolism and Pertussis Toxin production.

The production of acellular pertussis in comparison with whole cell pertussis vaccines demands 5-25 times the amount of Bordetella pertussis' virulence factors, such as Pertussis Toxin (PT), to produce the same number of vaccine doses. An increase in the volumetric productivity by employing fed-batch rather than the currently used batch cultivations of B. pertussis could reduce the cost price of acellular pertussis vaccines.

Effect of relevant culture parameters on Pertussis Toxin expression by Bordetella pertussis.

Whooping cough vaccines are produced using different ranges of cultivation conditions and medium compositions, which are known to influence growth rate, virulence factor production and degradation, as well as the virulence factors' association to the cell. This study quantifies the impact of individual parameters on Pertussis Toxin (PT) production, using an optimized chemically defined medium as starting point, rather than a complex medium. A number of chemicals that are identified affect both growth rate and virulence factor production, which occur at similar levels in various commonly used production media.

Advanced process monitoring: the ultimate alternative.

Parametric release has the possibility to be the ultimate alternative for the use of animal tests. It involves the release of a product using evaluation of tightly controlled physical parameters, without the performance of a test on the final product. This practice is strengthened if there is a lack of validity for the final test to indicate quality or consistency.