Purification of Conjugate Vaccines using Membrane Filtration 

There are significant opportunities for using ultrafiltration in the downstream processing of capsular bacterial polysaccharides and polysaccharide-protein conjugates used as vaccines against pneumococci and meningococci. This includes sterile filtration, concentration and buffer exchange, as well as the removal of residual free polysaccharides from the desired polysaccharide-protein conjugate formed via an appropriate coupling reaction. These conjugated vaccines provide much better immunization, particularly in young children and the elderly. The removal of free polysaccharides requires the use of large pore size ultrafiltration membranes or even small pore size microfiltration membranes given the high molecular weight of the free polysaccharides (from several hundred to several thousand kDa).  Sterile filtration has unique challenges due to the large size of the conjugated vaccine.  This project is focused on developing improved membrane systems for the downstream processing of high value polysaccharide conjugate vaccines.

 

Hadidi, M., J. J. Buckley, and A. L. Zydney, “Ultrafiltration behavior of bacterial polysaccharides used in vaccines,” J. Membrane Sci., 490: 294-300 (2015).

Hadidi, M., J. J. Buckley, and A. L. Zydney, “Effects of solution conditions on characteristics and size exclusion chromatography of pneumoccoal polysaccharides and conjugate vaccines,” Carbohydrate Polymers, 152: 12-18 (2016).

Hadidi, M., J. J. Buckley, and A. L. Zydney, “Effects of electrostatic interactions on the ultrafiltration behavior of charged bacterial polysaccharides,” Biotech. Prog., 32: 1531-1538 (2016).