Designing cell lines for viral vaccine production: Where do we stand?

Abstract

Established animal cells, such as Vero, Madin Darby canine kidney (MDCK) or chicken embryo fibroblasts (CEFs), are still the main cell lines used for viral vaccine production, although new "designer cells" have been available for some years. These designer cell lines were specifically developed as a cell substrate for one application and are well characterized. Later screening for other possible applications widened the product range. These cells grow in suspension in chemically defined media under controlled conditions and can be used for up to 100 passages. Scale-up is easier and current process options allow cultivation in disposable bioreactors at cell concentrations higher than 1 × 10(7) cells/mL. This review covers the limitations of established cell lines and discusses the requirements and screening options for new host cells. Currently available designer cells for viral vaccine production (PER.C6, CAP, AGE1.CR, EB66 cells), together with other new cell lines (PBS-1, QOR/2E11, SogE, MFF-8C1 cells) that were recently described as possible cell substrates are presented. Using current process knowledge and cell line development tools, future upstream processing could resemble today's Chinese hamster ovary (CHO) cell processes for monoclonal antibody production: small scale bioreactors (disposable) in perfusion or fed-batch mode with cell concentrations above 1 × 10(8) cells/mL.

Recombinant vesicular stomatitis virus expressing the spike protein of genotype 2b porcine epidemic diarrhea virus: A platform for vaccine development against emerging epidemic isolates

“…*p < 0.05 and **p < 0.01. exceeding 10 8 PFU/ml in BHK-21 cells. Together with the advantages that BHK21 cells can grow in suspension in disposable bioreactors at cell concentrations higher than 1 × 10 7 cells/mL (Genzel, 2015), recombinant VSV could be an ideal platform for conveniently preparing vaccines against emerging or reemerging PEDV. At present, it is still difficult to construct recombinant PEDV using reverse genetics.…”

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

“…live-attenuated vaccines, inactivated vaccines, subunit/ recombinant/polysaccharide/conjugate vaccines, toxoid vaccines, the first three types are suitable to be manufactured using the cell-based approach. Several animal cells have been used for vaccine production for years, such as African green monkey kidney (Vero) cells that were used to produce vaccines against polio and rabies, Madin Darby canine kidney (MDCK) cells that were employed to manufacture influenza vaccines, and chicken embryo fibroblasts (CEFs) that were used to produce vaccines against measles, mumps, rabies and tick-borne encephalitis (Genzel 2015). As one successful example, IMOVAX V R Polio is a sterile suspension of types 1-3 of inactivated poliomyelitis vaccine and prepared from poliovirus cultured in Vero cells, which has been widely used to prevent poliomyelitis for both primary immunization and boosters through stimulating antibody production in the body.…”

Cell substrates for the production of viral vaccines

“…Such limitations, combined with the appearance of new technologies for cell line development, have encouraged the establishment of new cell lines, including the so-called "designer" cell lines [19,20]. Several ways have been explored to obtain the currently available new cell substrates, including selection pressure (e.g.…”