title: Cultivation of Mycobacterium bovis BCG in bioreactors.
abstract: The Mycobacterium bovis BCG vaccine for commercial use is classically produced as surface pellicles by culture on synthetic medium. Under these conditions, reproducibility of the cultures and quality assessment are hampered by slow growth of the bacilli, the formation of bacterial aggregates and a high proportion of dead bacilli after processing and final formulation of the vaccine. Here, we established dispersed cultures of M. bovis BCG in synthetic media in small-scale bioreactors. These cultures allow recording and adjusting of culture parameters and give rise to single bacilli with a high degree of live bacteria. In the murine model, bioreactor-grown M. bovis BCG exhibited slightly stronger replication and persistence than the vaccine produced under the classical conditions. The protective efficacy against challenge with M. tuberculosis was identical for both vaccine preparations.
authors.affiliation: Chiron Behring GmbH & Co., D-35006, Marburg, Germany. guido.dietrich@bernabiotech.com
authors.forename: Guido
authors.initials: G
authors.lastname: Dietrich
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.forename: Heinz
authors.initials: H
authors.lastname: Weber
authors.forename: Bernhard
authors.initials: B
authors.lastname: Knapp
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Diehl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hess
authors.forename: Friedrich
authors.initials: F
authors.lastname: Blackkolb
authors.forename: Michael
authors.initials: M
authors.lastname: Bröker
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Erika
authors.initials: E
authors.lastname: Hundt
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D019149:Bioreactors / Q000592:standards; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008858:Microscopy, Phase-Contrast; D009163:Mycobacterium bovis / Q000166:cytology* / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000254:growth & development; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D001500:BCG Vaccine