1. 0 HHS Influenza Vaccine Projects for NVAC Meeting November 29-30, 2005 By: Dr. Robin Robinson Sr. Project Officer ORDC/OPHEP/DHHS

2. 1 Overview Key Summer/Fall Events H5N1 Vaccine: Pre-Pandemic Vaccine Stockpile H5N1 + Alum Adjuvant Vaccine Candidates Egg-based Influenza Vaccine Contract: Egg Supply & H7N7 Vaccine Cell-based Influenza Vaccine Contract: PER.C6 Cell Line RFP 05-04 Cell- & Recombinant-based Influenza Vaccines RFP 05-08 Optimization of Influenza Vaccine Antigen

3. 2 Key Summer/Fall Influenza Events Results of NIAID/NIH clinical studies with H5N1 vaccine (antigen alone) Origin of 1918 pandemic influenza virus Emergence of H5N1 virus clade 2 isolates in Eurasia Emergence of drug-resistant H5N1 virus mutants to oseltamivir U.S. Pandemic Plan & Budget release U.S. pandemic models presented 2006 Preview: Year of the Adjuvant

4. 3 H5N1 Vaccine: Pre-Pandemic Vaccine Stockpile HHS Pandemic Plan goal: establish & maintain pre-pandemic vaccine stockpile for 20 M persons in critical workforce & high priority groups Contracts awarded for commercial scale production of egg-based inactivated monovalent split H5N1 bulk vaccine during seasonal vaccine manufacturing off-season to establish stockpile oSP: 0.33 M doses @ 90 ug HA/dose Sept. 04; completed Nov. 04 oSP: ~ 5.5 M doses @ 90 ug HA/dose Sept. 05; completion Dec. 05 oChiron: 2.0 M doses @ 90 ug HA/dose Oct. 05; completion Feb. 06 Manufacturing virus reference strain: reverse genetics reassortant avian influenza A/H5N1/Vietnam/2004/1203 x PR8 (St. Jude) Indemnification issued to St. Jude and SP in summer 2005 Formulation and fill finish of H5N1 + adjuvant vaccines await results of NIAID/NIH clinical studies in 2006

5. 4 H5N1 + Alum Adjuvant Vaccine Candidates Binding studies of H5N1 vaccine antigen to aluminum hydroxide indicate tight and rapid binding Formulation of commercial scale H5N1 bulk vaccine with aluminum hydroxide completed in Nov. 05 Fill finish mfg. of six formulations of H5N1 +/- alum vaccine completed in Nov. 05 NIAID/NIH expected to commence clinical studies with H5N1 +/- alum vaccine in early 2006 for safety and immunogenicity

6. 5 Egg-based Influenza Vaccine Contract: Egg Supply & H7N7 Vaccine Contract awarded Sept. 2004 to Sanofi Pasteur for establishment of secure, year-round embryonated hen’s eggs and other essential supplies for five years Transition from 9-month egg production cycle to year-round egg supply completed successfully Apr. 2005 Other essential supplies stockpiled in 2005 Establishment of contingency flocks in 2006 Production of pilot investigational lots of H7N7 + alum adjuvant vaccine in progress for safety & immunogenicity evaluation in clinical trials by NIAID/NIH VTEUs in 2006

7. 6 Cell-based Influenza Vaccine Contract: PER.C6 Cell Line Contract awarded Apr. 2005 to sanofi pasteur over five years to facilitate advanced development of a PER.C6 human cell-based influenza vaccine U.S. towards U.S. licensure in U.S. mfg facilities with surge capacity of 300 M monovalent doses of pandemic vaccine (15 ug/dose) Manufacturing of pilot investigational lots near completion in France for safety & immunogenicity clinical evaluation in U.S. Phase I studies scheduled for 2006

8. 7 RFP 05-04 Cell- & Recombinant- based Influenza Vaccines Goal: Expansion and acceleration of influenza vaccine surge capacity & diversification of influenza vaccine Solicitation for contract proposals to facilitate development of cell- or recombinant-based seasonal and pandemic influenza vaccines towards U.S. licensure and manufacturing Surge capacity of 150 M doses of pandemic vaccine RFP issued April 29, 2005 Proposals evaluated for technical merit Contracts under negotiation with Offerors Contract awards awaiting pending U.S. Congressional approval of Pandemic Appropriation Bill

9. 8 RFP 05-08 Optimization of Influenza Vaccine Antigen Solicitation for contract proposals to facilitate development of adjuvant and biological products, medical devices, and/or methods that optimize influenza HA antigen in vaccines to stretch the influenza vaccine supply Scope includes: oAdjuvants oImmune cytokines oAlternative delivery devices oOther delivery methods Synopsis issued March 17, 2005 RFP issuance expected December 2005 Contract awarding expected in 2Q06