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Updated: Mar 31, 2026

A Novel Bioreactor for High Density Cultivation of Diverse Microbial Communities
Published on: December 25, 2015
The use of dissolved oxygen-controlled, fed-batch aerobic cultivation for recombinant protein subunit vaccine
Patrick Farrell1, Jacob Sun1, Paul-Philippe Champagne1
1Bioprocess Research and Development, Sanofi Pasteur, 1755 Steeles Avenue West, Toronto, Canada M2R 3T4.
Abstract:
A simple "off-the-shelf" fed-batch approach to aerobic bacterial cultivation for recombinant protein subunit vaccine manufacturing is presented. In this approach, changes in the dissolved oxygen levels are used to adjust the nutrient feed rate (DO-stat), so that the desired dissolved oxygen level is maintained throughout cultivation. This enables high Escherichia coli cell densities and recombinant protein titers. When coupled to a kLa-matched scale-down model, process performance is shown to be consistent at the 2L, 20L, and 200L scales for two recombinant E. coli strains expressing different protein subunit vaccine candidates. Additionally, by mining historical DO-stat nutrient feeding data, a method to transition from DO-stat to a pre-determined feeding profile suitable for larger manufacturing scales without using feedback control is demonstrated at the 2L, 20L, and 200L scales.
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