Evaluation of anthrax vaccine production by Bacillus anthracis Sterne 34F2 in stirred suspension culture using a miniature bioreactor: A useful scale-down tool for studies on fermentations at high containment

The licensed UK anthrax vaccine is produced by static cultures of Bacillus anthracis Sterne 34F2 in glass Thompson bottles, each batch consisting of multiple bottles grown for 24–28 h. In this work, a novel miniature bioreactor was used as a scale-down tool to investigate the possible transfer of anthrax vaccine production from static culture to stirred tank operation and to explore the effects of this change in culture conditions on process performance. It is shown that the change to stirred culture conditions is possible and that the concentration of the two main vaccine components, Protective Antigen (PA) and Lethal Factor (LF), are reached in less than half the time compared to standard Thompson bottle methods. Furthermore, because higher cell densities were attained in the miniature bioreactor, a 74% increase in antigen concentration was achieved. More detailed analysis of the stirred bioreactor results operated with and without aeration showed antigen degradation in the presence of aeration. Overall this work demonstrates the usefulness of miniaturisation techniques to perform process characterisation studies safely and without significant capital investment for large-scale containment.