Although the threat of avian influenza has only recently made major media headlines, Europe began developing its defences many years ago through the FLUPAN project which has now been completed. In September 2001, a team of scientists from the UK, Italy and Norway collaborated with vaccine researchers from Sanofi Pasteur in France on the FLUPAN project. Funded through the Fifth Framework Programme ‘Quality of Life and Management of Living Resources’ (QLK2-CT-2001-01786), the project aimed to develop a candidate vaccine for human pandemic flu. The partners decided to target the H7N1 avian influenza subtype which caused lethal outbreaks in Italian poultry in 1999. In 2003, 80 people in the Netherlands were infected with the related H7N7 subtype caught from poultry; one person died of the disease. It is thus conceivable that H7 subtypes could also cause a pandemic.

A highly pathogenic H7N1 virus (A/chicken/Italy/13474/99) isolated from Italian poultry was chosen for the FLUPAN project. The virus was too dangerous for standard influenza vaccine production, so the H7 haemagglutinin protein was altered by reverse genetics to make the virus safe. This process also modified the virus so that it could be grown in a mammalian cell line as well as the more usual poultry eggs. The FLUPAN vaccine virus (RD3) was therefore rescued on Vero cells, passaged on PER.C6 cells and safety tested in the NIBSC BSL4 facility. The RD3 virus was antigenically like the original A/chicken/Italy/13474/99 virus. Inactivated, split, alum adjuvanted PER.C6 grown RD3 vaccine was produced by sanofi pasteur and after pre-clinical testing at NIBSC and the University of Bergen, it was clinically evaluated in Bergen. In mice and ferrets, the vaccine induced low to moderate antibody responses yet the animals were protected against challenge with highly pathogenic H7N1 virus; in humans the vaccine was well tolerated and induced low antibody responses which were augmented by the addition of aluminium hydroxide adjuvant.The NIBSC contribution to FLUPAN was presented at Options for the Control of Influenza VI, Toronto, 2007.

NIBSC was the coordinator of FLUPAN and the partners were as follows: University of Reading ; Istituto Superiore di Sanita ; Health Protection Agency ; sanofi pasteur ; University of Bergen .

The FLUPAN project has done more than produce a potential vaccine against H7 avian influenza. In other strands of this research, surveillance of avian influenza viruses in Italy has enabled the partners to build up a library of reagents which will be a valuable resource for pandemic vaccine development in the future; new tests to monitor antibodies induced by avian influenza viruses have been developed which should improve our ability to detect emergence of new pandemic viruses.

At the start of the FLUPAN project, we were ill-prepared to react to the emergence of highly pathogenic avian influenza viruses in man. Reverse genetics technology had never before been used to produce influenza vaccine viruses and there was little experience in producing and testing potential pandemic vaccines. FLUPAN has paved the way in developing our pandemic preparedness and the resulting vaccine was the first influenza pandemic vaccine produced entirely in mammalian cells