Bio/Technology
13, 170 - 174 (1995)
doi:10.1038/nbt0295-170
Recent Advances in the Large Scale Fermentation of Neisseria meningitidis Group B for the Production of an Outer Membrane Protein ComplexJeffrey Fu1, *, F. James Bailey1, Joseph J. King2, Charles B. Parker1, R.S. Robin Robinett1, D. Garrett Kolodin3, Hugh A. George1
& Wayne K. Herber1
1Department of Virus & Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.
2Department of Bioproeess Research & Development, Merck Research Laboratories, West Point, PA 19486, USA.
3Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
*Corresponding author. The Outer Membrane Protein Complex (OMPC) of the bacterium Neisseria meningitidis group B has been used successfully as a protein carrier in a Haemophilus influenza type b (Hib) polysaccharide conjugate vaccine and a Streptococcus pneumoniae (Pn) polysaccharide conjugate vaccine to elicit anti-polysaccharide immune responses in young infants. The OMPC carrier is derived by detergent extraction of whole cells and, thus, the consistent generation of suitable biomass is central to an effective production process. Therefore, we have developed a large-scale, high-cell density (5 g/L dry cell weight) fermentation process for the cultivation of N. meningitidis B11. Since current requirements for the production of human biologies mandate strict control of all aspects of the manufacturing process, several key features of the process, including a chemically defined medium and a rational event-based harvest criterion, support current good manufacturing practice (cGMP) and increased productivity.
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