[Effect of the preservative thiomersal on the release of interleukin-1 beta from human peripheral blood cells]. / Einfluss des Konservierungsmittels Thiomersal auf die Interleukin-1 Beta Ausschüttung humaner peripherer Blutzellen.

Several vaccines have been tested in the human whole blood pyrogen test as an alternative to the rabbit pyrogen test. As reported previously by our group, the alternative test system is basically applicable to vaccines. The widely used conservative thiomersal is influencing the test system. Surprisingly, the induction of fever inducing cytokines by endotoxin contaminations and other pyrogens can be suppressed by thiomersal.

[Development of a novel influenza vaccine derived from a continuous cell line]. / Entwicklung eines neuen, aus permanenten Zellen gewonnenen Grippe-Impfstoffes.

Influenza viruses for production are presently produced in embryonated hen"s eggs. This conventional standard methodology is extremely cumbersome; it requires millions of eggs and an extensive purification to reduce the amount of contaminating egg proteins and to minimise the risk of allergies against egg albumin. The shortage of eggs in a pandemic situation, the selection of egg-adapted variants and the presence of adventitious viruses has emphasised the necessity for production of Influenza vaccines on a well characterised stable cell line. Our established serum and protein free Vero cell technology has been successfully adapted to large scale production of a huge variety of Influenza virus strains. The production in 1200 liter fermenter cultures under serum free conditions gave antigen yields comparable to the conventional embryonated egg technology. The development of a rapid and efficient purification scheme resulted in a safe high purity vaccine which was at least as immunogenic as conventional egg-derived vaccines in a mouse model. Clinical trials in the UK, Poland and Austria demonstrated that the Vero cell derived influenza vaccine is well tolerated, safe and highly immunogenic in humans.

Development of a Vero cell-derived influenza whole virus vaccine.

Influenza vaccine production is dependent on the availability of embryonated hen eggs for virus growth. This is an extremely cumbersome system with many disadvantages with respect to selection of virus variants and the presence of adventitious viruses. We have developed an alternative cell culture system which allows rapid production of large volumes of vaccine. The WHO-approved Vero cell line was used in serum-free culture to grow many influenza strains to high titre. This system could be scaled-up to allow vaccine production with a 1200 litre fermenter. A purification scheme was developed which resulted in a high purity whole virus vaccine. This was demonstrated to be at least as immunogenic as a conventional egg-derived preparation.

A novel mammalian cell (Vero) derived influenza virus vaccine: development, characterization and industrial scale production.

Influenza virus for vaccine production are presently produced in embryonated chicken eggs. This conventional standard methodology is extremely cumbersome; it requires a huge amount of eggs and an extensive purification to reduce the amount of contaminating egg proteins and to minimize the risk of allergies against egg albumin. The shortage of eggs in a pandemic situation, the selection of egg-adapted variants and the presence of adventitious viruses has emphasized the necessity for production of influenza vaccines on a well characterized stable cell line. Our established Vero cell technology has been successfully adapted to large scale production of a variety of influenza virus strains. The production in 1200 litre fermenter cultures under serum-free conditions gave antigen yields comparable to the conventional embryonated egg technology. The development of a rapid and efficient purification scheme resulted in a safe high purity vaccine which was at least as immunogenic as conventional egg-derived vaccines in a mouse model. This vaccine has been shown to be safe and highly immunogenic in chimpanzees and to be capable of protecting ferrets against challenge with live virus. Clinical trials have now been initiated in the UK and Austria.

Development of a mammalian cell (Vero) derived candidate influenza virus vaccine.

Influenza vaccine production is dependent on the availability of embryonated hen eggs for virus growth. This is an extremely cumbersome system with many disadvantages with respect to selection of virus variants and presence of adventitious viruses. We have developed an alternative cell culture system which allows rapid production of large volumes of vaccine. The World Health Organisation (WHO) approved Vero cell line was used in serum-free culture to grow a multitude of influenza strains to high titre. This system could be scaled-up to allow vaccine production with a 1200 litre fermenter volume. A purification scheme was developed which resulted in a high purity whole virus vaccine. This was demonstrated to be at least as immunogenic as a conventional egg-derived preparation in a mouse model.