call 2004: post-genomic approaches to a human pandemic influenza vaccine project title: live...

Call 2004: Post-genomic approaches to a human pandemic influenza vaccine Project title: Live attenuated replication-defective influenza vaccine, FLUVACCGrant: EUR 9.2 Mio. Program Start: Sept. 2005

BioTest, CZAnimal Trials

BIA Separations, SIVirus Purification

Medical University Vienna, AT

Robert Koch Institute, DEInfluenza B

AVIRGreen Hills Biotechnology

Coordination + ManagementReverse Genetics

Vaccine ProductionFormulation

GPC-Biotech, DEKinase Inhibitors

Institute of Influenza, RUSClinical Trials

Weikom, ATPublic Relations

SurgeryReverse Genetics

Clin. Pharm.Clinical Trials

VirologyInfluenza

Diagnostics

Vichem, HUKinase Inhibitors

Henogen, BEContract Manufacturer

FluVacc

FluVacc/Flureplication-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 trialPhase 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