Cultivation of Mycobacterium bovis BCG in bioreactors.
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.
Dietrich
Guido
G
Chiron Behring GmbH & Co., D-35006, Marburg, Germany. guido.dietrich@bernabiotech.com
Mollenkopf
Hans-Joachim
HJ
Weber
Heinz
H
Knapp
Bernhard
B
Diehl
Klaus-Dieter
KD
Hess
Jürgen
J
Blackkolb
Friedrich
F
Bröker
Michael
M
Kaufmann
Stefan H E
SH
Hundt
Erika
E
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
D001500:BCG Vaccine