van de Waterbeemd Bas, Streefland Mathieu, Pennings Jeroen, van der Pol Leo, Beuvery Coen, Tramper Johannes, Martens Dirk
Nederlands Vaccin Instituut (NVI), Unit Research and Development, PO Box 457, 3720 AL Bilthoven, The Netherlands.
Biotechnol Bioeng. 2009 Aug 1;103(5):900-8. doi: 10.1002/bit.22326.
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. A quantitative product quality score is calculated based on the expression levels of these virulence genes, which allows comparison of expected product quality between culture samples. Product quality scores were maximal throughout the logarithmic growth phase, but dropped significantly at the start of the stationary phase. This showed that the decreasing lactate and glutamate concentrations towards the end of the batch are critical for product quality. On-line measurement of these nutrients allows the cultivation process to be harvested at the optimal harvest point, increasing process robustness and consistency.
