Matrix and Backstage: Cellular Substrates for Viral Vaccines

Abstract

Vaccines are complex products that are manufactured in highly dynamic processes. Cellular substrates are one critical component that can have an enormous impact on reactogenicity of the final preparation, level of attenuation of a live virus, yield of infectious units or antigens, and cost per vaccine dose. Such parameters contribute to feasibility and affordability of vaccine programs both in industrialized countries and developing regions. This review summarizes the diversity of cellular substrates for propagation of viral vaccines from primary tissue explants and embryonated chicken eggs to designed continuous cell lines of human and avian origin.

Monitoring changes in proteome during stepwise adaptation of a MDCK cell line from adherence to growth in suspension

“…Viral vaccine production processes, however, still rely on primary cell lines (chicken embryo fibroblasts, primary monkey kidney cells), diploid cell lines (human embryonic lung tissue; WI-38, MRC-5) or continuous cell lines (Madin Darby canine kidney, MDCK; African green monkey kidney, Vero) with mainly adherent growth properties [3]. This is due to the risk involved in cell line adaptation to evolve undesired cell line properties, i.e.…”

“…These include the use of optimized media such as SFM4BHK21 medium (HyClone) or EX-CELL ® medium (Sigma-Aldrich) [5,9], the application of dynamic cultivation systems like spinner flasks [10] and/or genetic modifications [11][12][13][14][15] as well as the generation of so-called designer cells with specific growth properties [3]. For MDCK cells, an efficient host for influenza virus production [16,17], only few successful attempts to adapt cells to suspension growth have been reported [9,11,[18][19][20][21].…”

New York State Emergency Preparedness and Response to Influenza Pandemics 1918–2018

“…The propagation in embryonated chicken eggs [11] is still the most prevalent method for production. However, recent developments include an FDA-approved quadrivalent cell-based vaccine grown in the Madin Darby Canine Kidney (MDCK) cell line [12] and a trivalent recombinant influenza vaccine produced from a baculovirus expression vector in the Sf9 armyworm cell line [13]. These cell-based systems can be quickly scaled up for mass-production and circumvent the potential limited supply of eggs during pandemics when poultry availability may also suffer.…”

Cell substrates for the production of viral vaccines

“…The first cell substrates developed to this aim included both diploid and continuous cell lines (Table 1) [12]. Diploid cell lines, such as human lung-derived MRC5 (Medical Research Council 5) and WI-38 (Wistar Institute) cells [13,14], were obtained from primary cultures.…”