National Vaccine Advisory Committee June 7, 2005 Pandemic Influenza Vaccine Research and Development Linda C. Lambert Chief, Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/DHHS

Sanofi Pasteur H5 Vaccine Vaccine candidate manufactured using reverse genetics under NIH contract Inactivated vaccine received in March Adult trial began April at 3 VTEUs –7.5, 15, 45, 90 mcg vs. placebo; 2 doses Enrollment completed mid May Final results expected in late summer Separate trials planned in elderly and children, 2 dose regimen, dosage based on adult data

Chiron H5 Vaccine Vaccine candidate manufactured using reverse genetics under NIH contract 10,000 doses Vaccine anticipated late Fall 2005 Clinical trial plan: adults, elderly and children 2 dose regimen, ~ 1 month apart

H5 Vaccine Dose Optimization Strategies Route Intramuscular (IM) versus Intradermal (ID) administration of inactivated H5 vaccine. Phase I protocol filed to FDA Trial start date July (planned) Data expected Q Adjuvants Subcontract to Baxter to produce whole virus inactivated H5 vaccine (Vero) +/- alum Discussions with Chiron and Sanofi Pasteur ongoing

GSK TIV Clinical Trial NIAID rapidly initiated a Phase III trial to evaluate safety and immunogenicity of GSK’s inter-pandemic Fluarix® vaccine in healthy adults: -- Trial began in Dec subjects enrolled in 5 days -- Trial conducted through VTEUs -- BLA submitted May 25 th

Non-egg based technologies NIAID supports projects aimed at developing alternatives to production of influenza vaccine in eggs: - Recombinant protein - Virus-like particles - Cell culture-based technology - Alphavirus vector - DNA based vaccines