• Crucell is developing a yellow fever vaccine, Flavimun^®, based on the know how of the well-established vaccine formerly produced by the Robert Koch institute in Germany.
• The vaccine is very well tolerated, safe and highly immunogenic.
• Registration submission of Crucell's yellow fever vaccine is expected in 2008.

Since 1963, one of the most reliable vaccines for yellow fever has been produced by the Robert Koch Institute, Berlin. Over 2.5 million doses of the vaccine have been distributed. Based on attenuated viruses grown on chicken embryos, the vaccine is safe, highly immunogenic and well tolerated. Protection starts from ten days after a single dose and persists for ten years. Crucell is developing a yellow fever vaccine based on the know-how it has received from the Robert Koch Institute.

Currently there is only a single supplier for a yellow fever vaccine in private markets. Global shortages and out of stock situations show the need of an additional supplier of a safe yellow fever vaccine. The launch of Crucell’s yellow fever vaccine will not only provide a choice and higher security of supply but also increases the value of the existing travel vaccine portfolio of Crucell.

In a clinical phase III bridging study, the immunogenicity and safety of Crucell’s yellow fever vaccine was compared to the original RKI Yellow Fever vaccine and to the commercially available yellow fever vaccine Stamaril® (sanofi aventis).

All three vaccines elicited an effective immune response with seroprotection achieved in 100% of individuals in each vaccine group at a neutralizing antibody titer of ≥ 1:10. Crucell’s yellow fever vaccine was shown to be comparable to the other two vaccine products. As a result, the vaccine was concluded to be non-inferior to the other two vaccine products. In addition, at the ≥ 1:450 level, Crucell’s yellow fever vaccine was associated with a significantly higher seroprotection rate than Stamaril® (P=0.0025).

The immune response to Crucell’s yellow fever vaccine and RKI-YF was very similar, with no significant difference in antibody titer between the two groups. However, Stamaril® vaccination resulted in a significantly lower antibody titer (P<0.0001 versus the YF-vaccine of Crucell).

All three vaccines were well tolerated. The incidence of solicited local reactions in the Stamaril® group (36.8%) was comparable to that in the Crucell’s Flavimun® vaccine group (36.7%, P = 0.9794), but was significantly higher in the RKI-YF group (57.1%, P = 0.0032).

In summary, Crucell’s yellow fever vaccine has been proven to be highly immunogenic, safe and well tolerated. Additionally the manufacturing consistency of the vaccine has been demonstrated.

An infectious disease transmitted by mosquitoes, yellow fever is prevalent in tropical regions of Africa and South and Central America. Approximately 200,000 cases occur each year, with a mortality rate of 15 percent. Endemic areas have increased over the past twenty years, and because the yellow fever virus circulates in nature independently of humans, it has not been possible to eradicate it. Also there is a worldwide shortage in the supply of yellow fever vaccines.