A Combined Ultrafiltration/Diafiltration Process for the Purification of Oncolytic Measles Virus

Membranes

Daniel Loewe¹  Hauke Dieken¹  Peter Czermak¹  Tanja A. Grein¹  Denise Salzig¹ 

[1] Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, 35390 Giessen, Germany;

关键词: tangential flow filtration;    measles virus;    oncolytic virus;    continuous diafiltration;    discontinuous diafiltration;   

DOI  :  10.3390/membranes12020105

来源: DOAJ

【 摘 要 】

Measles virus (MV) is an important representative of a new class of cancer therapeutics known as oncolytic viruses. However, process intensification for the downstream purification of this fragile product is challenging. We previously found that a mid-range molecular weight cut-off (300 kDa) is optimal for the concentration of MV. Here, we tested continuous and discontinuous diafiltration for the purification of MV prepared in two different media to determine the influence of high and low protein loads. We found that a concentration step before diafiltration improved process economy and MV yield when using either serum-containing or serum-free medium. We also found that discontinuous diafiltration conferred a slight benefit in terms of the permeate flow, reflecting the repetitive dilution steps and the ability to break down parts of the fouling layer on the membrane. In summary, the combined ultrafiltration/diafiltration process is suitable for the purification of MV, resulting in the recovery of ~50% infectious virus particles with a total concentration factor of 8 when using 5 diavolumes of buffer.

【 授权许可】

Unknown