A study of the physiology of Bacillus anthracis Sterne during manufacture of the UK acellular anthrax vaccine

Aim:  To analyse the growth of Bacillus anthracis during simulations of the UK anthrax vaccine manufacturing process. Methods and Results:  Simulated vaccine production runs were performed using the toxigenic, acapsulate Sterne 34F2 strain of B. anthracis in semi-defined medium. After rising during the logarithmic growth phase, the pH of the culture starts to fall at about 18 h from pH 8·7 to reach <7·6 at 26 h, coincident with consumption of glucose and optimal production of protective antigen (PA; 7·89 g ml−1, SD 1·0) and lethal factor (LF; 1·85 g ml−1, SD 0·29). No increased breakdown of toxin antigens was seen over the 26–32 h period. When glucose was exhausted, amino acids (principally serine) were utilized as an alternative carbon source. Sporulation was not observed during the 32 h. Conclusions:  PA and LF, the principal constituents in the UK anthrax vaccine, undergo little degradation during vaccine fermentation. The vaccine manufacturing process is robust and reproducible. Significance and Impact of the Study:  This is the first detailed analysis of the manufacturing process used for the UK acellular anthrax vaccine; insight gained into the process will support continued and safe vaccine manufacture.