Development and scale-up of a fed-batch process for the production of capsular polysaccharide from Haemophilus influenzae.
The production of the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus influenzae type b is important for the production of effective conjugate vaccines. Factors limiting the production of this polysaccharide from H. influenzae type b in liquid culture were investigated. A fed-batch fermentation was developed that increased cell density and PRP titer approximately four fold when compared to the batch fermentation. This fed-batch process was successfully scaled from the 1.5 l development scale to the 500 l manufacturing scale. The maximum cell density in the 500 l fermentation was 6 g dry cell weight per liter and the PRP concentration was 1.3 g l(-1).
Merritt
J
J
University of Massachusetts Lowell, Department of Chemical and Nuclear Engineering, 1 University Avenue, Lowell, MA 01854, USA.
Allard
G
G
O'Toole
L
L
Swartz
R
R
Licari
P
P
D016667:Bacterial Capsules; D018929:Cell Culture Techniques / Q000379:methods; D005285:Fermentation; D018073:Haemophilus Vaccines / Q000096:biosynthesis*; D006193:Haemophilus influenzae / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D013242:Sterilization; D013997:Time Factors
D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial