Call 2004: Post-genomic approaches to a human pandemic influenza vaccine Project title: Live attenuated replication-defective influenza vaccine, FLUVACC Grant: EUR 9.2 Mio. Program Start: Sept BioTest, CZ Animal Trials BIA Separations, SI Virus Purification Medical University Vienna, AT Robert Koch Institute, DE Influenza B AVIR Green Hills Biotechnology Coordination + Management Reverse Genetics Vaccine Production Formulation GPC-Biotech, DE Kinase Inhibitors Institute of Influenza, RUS Clinical Trials Weikom, AT Public Relations Surgery Reverse Genetics Clin. Pharm. Clinical Trials Virology Influenza Diagnostics Vichem, HU Kinase Inhibitors Henogen, BE Contract Manufacturer FluVacc

FluVacc/ Flu replication-deficient intranasal influenza vaccine

FLU vaccine viruses are based on deletion of the interferon-antagonist NS1 wild-type NS1 FLU vaccine properties: Replication deficient safe Interferon induction immunogenic

Randomized, double blind, placebo-controlled Single immunization, dose escalation 48 male adult volunteers Primary objective: safety, tolerability Secondary objectives: immune response, PK (shedding) Results: no significant difference in adverse events compared to placebo no shedding of vaccine virus statistical significant immune response compared to placebo (p<0.001) vaccine induces cross-reactive neutralizing antibodies against drift variants Clinical trial Phase I seasonal FLU FLU vaccine is safe and immunogenic in humans

High immunogenicity strains generated Replication-defective phenotype in humans confirmed Effective intranasal delivery by spray device achieved Reverse genetics method developed Production in Vero cells established Method to increase viral yield developed Efficient and fast purification procedure developed Preliminary data clinical trial with pandemic FLU superior Results beyond state of the art