Evaluation of novel large cut-off ultrafiltration membranes for adenovirus serotype 5 (Ad5) concentration

Piergiuseppe Nestola, Duarte L. Martins, Cristina Peixoto, Susanne Roederstein, Tobias Schleuss, Paula M. Alves, José P B Mota, Manuel J T Carrondo

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The purification of virus particles and viral vectors for vaccine and gene therapy applications is gaining increasing importance in order to deliver a fast, efficient, and reliable production process. Ultrafiltration (UF) is a widely employed unit operation in bioprocessing and its use is present in several steps of the downstream purification train of biopharmaceuticals. However, to date few studies have thoroughly investigated the performance of several membrane materials and cut-offs for virus concentration/diafiltration. The present study aimed at developing a novel class of UF cassettes for virus concentration/diafiltration. A detailed study was conducted to evaluate the effects of (i) membrane materials, namely polyethersulfone (PES), regenerated cellulose (RC), and highly cross-linked RC (xRC), (ii) nominal cut-off, and (iii) UF device geometry at different production scales. The results indicate that the xRC cassettes with a cut-off of approximately 500 kDa are able to achieve a 10-fold concentration factor with 100% recovery of particles with a process time twice as fast as that of a commercially available hollow fiber. DNA and host cell protein clearances, as well as hydraulic permeability and fouling behavior, were also assessed.

Original languageEnglish
Article numbere115802
JournalPlosOne
Volume9
Issue number12
DOIs
Publication statusPublished - 29 Dec 2014

Fingerprint

Ultrafiltration
Adenoviridae
ultrafiltration
Viruses
serotypes
Membranes
Cellulose
Purification
cellulose
Viral Vaccines
bioprocessing
vector vaccines
Active Immunotherapy
Gene therapy
biopharmaceuticals
viruses
gene therapy
Viral Genes
fouling
Fouling

Cite this

Nestola, Piergiuseppe ; Martins, Duarte L. ; Peixoto, Cristina ; Roederstein, Susanne ; Schleuss, Tobias ; Alves, Paula M. ; Mota, José P B ; Carrondo, Manuel J T. / Evaluation of novel large cut-off ultrafiltration membranes for adenovirus serotype 5 (Ad5) concentration. In: PlosOne. 2014 ; Vol. 9, No. 12.
@article{f04ffac997c64af18a5458951a14ef29,
title = "Evaluation of novel large cut-off ultrafiltration membranes for adenovirus serotype 5 (Ad5) concentration",
abstract = "The purification of virus particles and viral vectors for vaccine and gene therapy applications is gaining increasing importance in order to deliver a fast, efficient, and reliable production process. Ultrafiltration (UF) is a widely employed unit operation in bioprocessing and its use is present in several steps of the downstream purification train of biopharmaceuticals. However, to date few studies have thoroughly investigated the performance of several membrane materials and cut-offs for virus concentration/diafiltration. The present study aimed at developing a novel class of UF cassettes for virus concentration/diafiltration. A detailed study was conducted to evaluate the effects of (i) membrane materials, namely polyethersulfone (PES), regenerated cellulose (RC), and highly cross-linked RC (xRC), (ii) nominal cut-off, and (iii) UF device geometry at different production scales. The results indicate that the xRC cassettes with a cut-off of approximately 500 kDa are able to achieve a 10-fold concentration factor with 100{\%} recovery of particles with a process time twice as fast as that of a commercially available hollow fiber. DNA and host cell protein clearances, as well as hydraulic permeability and fouling behavior, were also assessed.",
author = "Piergiuseppe Nestola and Martins, {Duarte L.} and Cristina Peixoto and Susanne Roederstein and Tobias Schleuss and Alves, {Paula M.} and Mota, {Jos{\'e} P B} and Carrondo, {Manuel J T}",
note = "WOS:000347120200071",
year = "2014",
month = "12",
day = "29",
doi = "10.1371/journal.pone.0115802",
language = "English",
volume = "9",
journal = "PlosOne",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

Evaluation of novel large cut-off ultrafiltration membranes for adenovirus serotype 5 (Ad5) concentration. / Nestola, Piergiuseppe; Martins, Duarte L.; Peixoto, Cristina; Roederstein, Susanne; Schleuss, Tobias; Alves, Paula M.; Mota, José P B; Carrondo, Manuel J T.

In: PlosOne, Vol. 9, No. 12, e115802, 29.12.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of novel large cut-off ultrafiltration membranes for adenovirus serotype 5 (Ad5) concentration

AU - Nestola, Piergiuseppe

AU - Martins, Duarte L.

AU - Peixoto, Cristina

AU - Roederstein, Susanne

AU - Schleuss, Tobias

AU - Alves, Paula M.

AU - Mota, José P B

AU - Carrondo, Manuel J T

N1 - WOS:000347120200071

PY - 2014/12/29

Y1 - 2014/12/29

N2 - The purification of virus particles and viral vectors for vaccine and gene therapy applications is gaining increasing importance in order to deliver a fast, efficient, and reliable production process. Ultrafiltration (UF) is a widely employed unit operation in bioprocessing and its use is present in several steps of the downstream purification train of biopharmaceuticals. However, to date few studies have thoroughly investigated the performance of several membrane materials and cut-offs for virus concentration/diafiltration. The present study aimed at developing a novel class of UF cassettes for virus concentration/diafiltration. A detailed study was conducted to evaluate the effects of (i) membrane materials, namely polyethersulfone (PES), regenerated cellulose (RC), and highly cross-linked RC (xRC), (ii) nominal cut-off, and (iii) UF device geometry at different production scales. The results indicate that the xRC cassettes with a cut-off of approximately 500 kDa are able to achieve a 10-fold concentration factor with 100% recovery of particles with a process time twice as fast as that of a commercially available hollow fiber. DNA and host cell protein clearances, as well as hydraulic permeability and fouling behavior, were also assessed.

AB - The purification of virus particles and viral vectors for vaccine and gene therapy applications is gaining increasing importance in order to deliver a fast, efficient, and reliable production process. Ultrafiltration (UF) is a widely employed unit operation in bioprocessing and its use is present in several steps of the downstream purification train of biopharmaceuticals. However, to date few studies have thoroughly investigated the performance of several membrane materials and cut-offs for virus concentration/diafiltration. The present study aimed at developing a novel class of UF cassettes for virus concentration/diafiltration. A detailed study was conducted to evaluate the effects of (i) membrane materials, namely polyethersulfone (PES), regenerated cellulose (RC), and highly cross-linked RC (xRC), (ii) nominal cut-off, and (iii) UF device geometry at different production scales. The results indicate that the xRC cassettes with a cut-off of approximately 500 kDa are able to achieve a 10-fold concentration factor with 100% recovery of particles with a process time twice as fast as that of a commercially available hollow fiber. DNA and host cell protein clearances, as well as hydraulic permeability and fouling behavior, were also assessed.

UR - http://www.scopus.com/inward/record.url?scp=84920070336&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0115802

DO - 10.1371/journal.pone.0115802

M3 - Article

VL - 9

JO - PlosOne

JF - PlosOne

SN - 1932-6203

IS - 12

M1 - e115802

ER -