Ultrafiltration behavior of bacterial polysaccharides used in vaccines

Ultrafiltration is widely used for the purification of polysaccharide based vaccines against pneumococci and meningococci, but there is currently no fundamental understanding of the factors controlling the ultrafiltration behavior of these polysaccharides. Experiments were performed using purified pneumococcus polysaccharides (serotypes Pn3, Pn9V, and Pn14) provided by Pfizer. Ultrafiltration data were obtained in a stirred cell using Ultracel (TM) composite regenerated cellulose and Biomax (TM) polyethersulfone membranes with different nominal molecular weight cutoffs. Polysaccharide transmission was a strong function of filtrate flux, with data at low bulk concentrations in good agreement with the classical concentration polarization model. Polysaccharide fouling became significant at high filtrate flux during ultrafiltration or more concentrated solutions, consistent with the presence of a critical value for the wall concentration. Polysaccharide transmission was in good agreement with available hydrodynamic models accounting for the presence of a pore size distribution, with the effective size of the polysaccharide determined by dynamic light scattering or size exclusion chromatography. These results provide important insights into the factors controlling the ultrafiltration behavior of bacterial polysaccharides of interest in bioprocessing applications. (C) 2015 Elsevier B.V. All rights reserved.