The manufacture of live vaccines (such as measles or smallpox vaccines) is in practice a very complicated process, amongst other things, because of the number of regulations with which the manufacturer must comply. In principle, however, the production process itself is quite simple.
Enrichment of the vaccine virus Production is started by adding a small quantity of the relevant virus stock solution or “working seed virus” to a suitable cell culture. The virus penetrates and infects the cells. Because the vaccine virus has been adapted to growing in the particular cell culture used, it will start replicating immediately. In a short time a large number of copies of the virus, identical to the stock virus solution, will be present in the infected cells. This part of the production process is called growth or enrichment of the vaccine virus.
Harvesting of the vaccine virus Some viruses are able to leave the cell on their own. However, this is not common for all. In these situations it is necessary to help the virus out of the cell by destroying the cell membrane. This is called harvesting the vaccine virus. Harvesting results in a solution that contains a large amount of the virus but also unwanted by-products (impurities), including debris from the host cells. In biotechnology process terminology, enrichment and harvesting of the vaccine virus is called the “upstream process”.
Purification The next phase in the production process is to remove the unwanted by-products so that the virus solution is pure and well-characterised. This occurs in a purification process consisting of one, or more often, several steps and is known as the “downstream process”. The resulting product from this process is a “raw vaccine” (or bulk vaccine) where the vaccine virus exists in a very high concentration without the presence of impurities. The raw vaccine can be stored in a liquid form or, for a longer period of time, frozen at - 20 °C or - 80 °C, until its final treatment.
Final treatment of the vaccine Final treatment of the vaccine consists of producing a suitable final solution and if necessary, adding substances that stabilise the vaccine and make it suitable.
