Cell-Culture-Based Vaccine ProductionCell-culture-based technology is robust and reliable and could become a practical alternative for the pharmaceutical industry in vaccine production. Once the virus is propagated and harvested, the downstream processing parameters for purification, filling, and packaging of the vaccine are similar to current pharmaceutical methodologies and egg-based methodologies. However, there are no lead times involved, because typical cell-culture processes use cell lines; once a cell line is infected with the seed virus in a fermenter, the process can begin. The critical step is the availability of the seed virus. The substrates or media for cell-line propagation are not susceptible to virulent virus strains as embryonated chicken eggs are.
The cell-culture vaccine process is suitable for large-scale manufacture, and the process parameters can be ramped up and run routinely and cost effectively. The typical cell-culture production process can be run in batch sizes of practical scale, sufficient to provide vaccine quantities for interpandemic periods and pandemics. However, to date, no vaccines have been licensed using this technology.
Chiron has already submitted “mock-up” dossiers to European Union (EU) regulatory authorities for review and approval of an avian influenza vaccine (currently in clinical trials) and a license application for a cell-culture-based vaccine. This paper is focused on the cell-culture vaccine manufacturing process used by Chiron, as well as the use of adjuvants to enhance immunogenicity and reduce dosage size.
Examples
Vaccines for
polio, measles, mumps, rubella, and chickenpox are currently made in cell cultures. Due to the
H5N1 pandemic threat, research into using cell culture for influenza vaccines is being funded by the United States government. Novel ideas in the field include recombinant DNA-based vaccines, such as one made using human adenovirus (a common cold virus) as a vector,
or the use of adjuvants.
potential of cell based vaccines
The cell-culture process for influenza vaccines offers high potential as an alternative method to egg-based production. Cell culture has the capability to offer a predictable, rapid and responsive method for production of well-tolerated and effective vaccines, with low levels of adverse events similar to egg-based vaccines.
Cell-culture materials can be stored, so the production process can be initiated at any time. In addition, production can be scaled up in response to increased vaccine demand. As circulating influenza virus strains are continually changing, the viruses used to produce vaccine must also change to match the circulating strain. Due to the short lead time for production, such virus strain changes can be incorporated in the cell culture-based production more rapidly than for egg-based vaccines.
In addition, cell culture may also allow wild-type influenza virus-isolates of a pandemic virus to be safely propagated, and result in high virus titres as viral propagation and purification are performed in closed production systems. The use of wild-type virus could also shorten the time needed to produce the vaccine in a pandemic situation as cell culture offers a short lead time for production and eliminates the need to produce virus strains which are attenuated to non-pathogenicity for eggs.
Cell culture-based vaccines are produced in well-defined and well-investigated cell substrates, which are required to be free of external contaminating agents before being approved for use in vaccine manufacturing. Therefore, cell cultures approved for influenza vaccine production offer an excellent alternative to the currently used pharma-grade embryonated hen eggs. As cell culture-based vaccines do not contain any egg proteins they may be recommended for people with egg allergies.
Importantly, clinical studies with cell culture-based influenza vaccines have shown that they are of high quality and meet the efficacy requirements set out by EU regulatory authorities for cell culture-based vaccines.
