Current egg-based manufacturing methodologies for the production of influenza vaccines are slow and have an inherent lag period from variant identification to vial. In addition, seasonal influenza variants are predicted up to 12 months in advance by the World Health Organization but may only be confirmed five to six months before a vaccine reaches the market. Vaccine manufacturers have little time to produce and stockpile the selected candidates, and often have to manufacture one or more vaccine strains in advance at risk of the preferred strains altering. There is a need for a more flexible and rapid production methodology to produce cheap and effective influenza vaccines with minimal notice for pandemic variants. A new approach to combat this threat is required. There are several technologies in early development that may offer a more viable solution to the pandemic threat, such as the use of microbial-derived production processes and platform virus-like particle manufacturing strategies to alleviate some of these constraints and lead to a more rapid response time.
Vaccination—Supply and Demand
The original licensed influenza vaccines were inactivated versions of a mixture of three influenza strains produced by an egg-based manufacturing process. To give an idea of scale, on average, between one and two eggs are needed to produce one dose of vaccine. During the production process itself, fertile hen eggs are infected with the candidate influenza strain and incubated for several days. The vaccine is purified from the allantoic fluid of virus-infected chick embryos by a combination of tangential flow filtration (TFF), density centrifugation, and, more recently, by anion exchange column chromatography. The virus is also chemically inactivated through formaldehyde or β-propiolactone treatment at some point during processing.
More recently, licensed inactivated influenza vaccines are made in mammalian cell culture and purified by more modern techniques. The major hurdle facing the manufacturers for the production of a pandemic vaccine is the time of production with the entire production process for a season's influenza vaccine taking an average of six months. The challenge to the vaccine producers is to develop a production process with a rapid turnaround time with minimal notice to combat a pandemic threat.
There are many approaches that may be taken for the development and production of a vaccine. An attractive prospect is the use of platform production systems which, in turn, would offer significant advantages for the production of pandemic vaccines, significantly reducing the lead in and production times and ultimately time to patient once the virus serotype has been identified. This approach will also allow for strategic manufacturing sites to be at a state of operational readiness for the production of the vaccine candidate with minimal notice. One such approach is the use of a microbial system for the production of virus-like particle (VLP) based vaccines.