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Challenges for the production of human influenza vaccines
Today, in addition to seasonal human influenza vaccines, prepandemic and pandemic vaccines are required. Seasonal vaccines consist of three different influenza subtypes that are updated every influenza season for the Northern and Southern hemispheres. Currently, the composition comprises two influenza A strains: H1N1 and H3N2, and one influenza B strain. Seasonal vaccines for the Northern hemisphere are manufactured to be available for the next influenza season, starting production in early spring each year and delivering the vaccine in autumn for vaccination [1,2]. Typically, mostly elderly people, children and immunocompromised individuals are vaccinated.
Based on the potential threat of an avian or swine influenza pandemic, preparedness plans have been developed by the WHO and national authorities. One concern is the lengthy time window required for vaccine manufacturing. Production of a suitable vaccine will require at least 3-4 months if a high-yield seed virus is available. A pandemic will probably not take more than 3 months to spread to all continents. Therefore, the production of prepandemic vaccines is also discussed. A prepandemic vaccine is a vaccine containing antigens that correspond to influenza strains thought to be most likely to cause a pandemic. Here, vaccine doses are to be stockpiled and in the case of a pandemic immediate vaccination can begin. Alternatively, individuals might be vaccinated upfront of a pandemic and, in cases of a pandemic, receive a booster vaccination to increase the respective immune response. However, all these measures depend on a sufficient level of cross-reactive protection [3]. Based on the experiences of early 2009, prepandemic vaccine stockpiles should contain H5N1 as well as H1N1 strains.
Pandemic vaccines need to be produced as soon as the emerging virus of the next pandemic has been isolated. Typically, they consist of only one virus strain. Approaches for the production of H5N1 vaccines consisted of methods based either on conventional reassortant generation or reverse genetics [4], or relied on the growth of wild-type viruses in biosafety level (BSL)-3+ facilities [5]. Currently, approaches with either 12-, 8- or 4-plasmid reverse genetics systems are used for the generation of high-yield production strains [6]. The lower the number of plasmids needed, the fewer problems are encountered with respect to transfection efficiency. In addition, an...