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Abstract:
A general introduction on virus vaccine production is given by discussing economical and social aspects of vaccines (top producers & vaccines) and presenting an overview on vaccine types, host cells and viruses. Terms like master and working cell bank as well as master and working virus seed are explained and the requirements for a successful vaccine are considered.
The use of primary, diploid or continuous (transformed) cell lines as host for the production of viral vaccines are compared. For each cell line (e.g. adherent or suspension), virus type and vaccine definition (live attenuated, inactivated, purified subunits, recombinant antigens) a specific production and purification process has to be established. Biphasic processes with a separate cell growth and virus production phase are discussed versus monophasic processes with the virus replication coupled to the cell growth. Examples of production schemes for polio, rabies and mink enteritis are shown. Media compositions and feeding strategies have to be selected as well as the production vessel, production conditions and the type of process.
Different typical issues that can be considered during virus production processes are discussed in detail for the influenza virus production in a microcarrier system as an example. Special focus will be on:
- mock infection against infection,
- influence of the multiplicity of infection,
- time-point of harvest
- factors that influence virus yield,
- serum-containing against serum-free media,
- cell metabolism,
- but also on the use of roller bottles, stirred tank bioreactors or wave bioreactors.
