Preparing for Pandemic Influenza

1. Priority Medicines for Europe and the World Preparing for Pandemic Influenza Anna Lönnroth European Commission DG Research: Health Research

2. Chapter 6.2 Pandemic Influenza Background paper prepared by DavidFedson, M.D., in collaboration with the WHO Global Influenza Programme

3. Influenza virus (Paul Digard, Dept Pathology, University of Cambridge)

4. Viral Replication

5. Annual influenza epidemics 3-5 million cases of severe illnessSignificant mortality among the elderly and in developing countriesEnormous health care costs, economic loss and work absenteeismCurrent vaccines about 70 % protective

6. Antigenic drift & shift drift shift (Albert Osterhaus, Erasmus University, Rotterdam, Netherlands)

7. 1918 A U.S. Army influenza ward in Luxembourg, during the 1918 epidemic. Photo courtesy National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, D.C.

8. Deaths from infectious diseases in USA Deaths from infectious diseases fell in the United States during the 20th century. The spike shows the 1918 influenza pandemic, which killed more than 40 million people, include about 500,000 Americans. Graph: CDC.

9. Past Influenza Pandemics 1918“Spanish flu”Killed 40-50 millionH1N1 1968“Hong Kong flu” killed 46.000H3N2 1997“Hong Kong”First Human H5N1 (killing 6/18) 1957“Asian flu” killed 98.000H2N2

10. Man as a mixing vessel Re-assortant virus Human virus Avian virus Avian virus (Albert Osterhaus, Erasmus University, Rotterdam, Netherlands)

11. Future Influenza Pandemics Between 1997 and 2004, the H5N1 strain has gained in pathogenicityH5N1 re-emerged in Vietnam in late 2003, killing about 70% of the infectedPossible human-human transmission of H5N1 in Thailand September 2004?H9N2 – Hong KongH7N7 – Netherlands Next?

12. Worst case scenario Pandemic of human-adapted avian influenza such as the 1997 H5N1 strain Could easily reach mortality rate of 30-40%Within a few months, 25% could have been infectedOver 1/2 billion deaths …or worse

13. Pandemic planning Lessons learned form SARS outbreakIdentify strategies to “buy time”Crisis management Planning in the interpandemic period

14. Limitations of current influenza vaccine Influenza vaccine needs to be reformulated with each epidemic Prediction & public health intervention in advance difficult Vaccine production up-scaling capacity insufficient & access inequity Low vaccine uptake although cost-effective (< 20% of expected) Available production technology inadequate for pandemic vaccine? Delayed vaccine production

15. What about treatment? 1. Vaccination is by far the most efficient way to control influenza2. Currently available drugs are not very efficient, but may become important in reducing mortality and prevent transmission (M2 inhibitors + Neuraminidase inhibitors)3. Production capacity insufficient to meet sudden demands + access inequity

16. SHORT term R&D Evaluate immunogenicity and safety of different monovalent, low-dose, adjuvanted ‘pandemic like’ vaccines and vaccination scheduled (avian HA)Develop ‘antigen sparing’ strategiesEvaluate safety and effectiveness of Reverse Genetics + resolve IPR & regulatory issues Prepare reagent libraries to speed up vaccine testingDevelop vaccine production technologies

17. SHORT term R&D Explore expansion of interpandemic use and manufacturing capacityDevelop more efficient anti-viral drugsInvestigate mechanisms of drug resistanceDevelop & evaluate non-medical control measuresAssess impact of common medications on clinical course of influenza-related illnessStudy the public health impact of vaccination

18. LONG term R&D Develop broad spectrum vaccines that provide long lasting protection (conserved antigens)Explore further DNA-based vaccinesContinue to develop anti-viral drugs…underpinned by basic immunology on vaccine response, pathophysiology & host defenceEnsure availability of effective antibioticsEvaluate long-term adverse events

19. Industrial hurdles Only 300 million vaccine doses are currently produced each year (trivalent)Upscaling challenges: - Market insufficiency - Market uncertainty - Stockpiling impossible- Regulatory & liability issues

20. Incentives needed Research & Development IPR on Reverse Genetics TechnologyAddress liability issues“GMO” concerns Current capacity and resources do not match needs for pandemic planning

21. Why Europe? 2/3 of the world’s influenza vaccine producers are located in Europe

22. EC Research Funding

23. FLUPAN Reverse genetics technology to develop reference strains of (avian) vaccine viruses Production of pilot lots in cell culture systems Immunogenicity/Safety evaluation in Phase I/II clinical trials Libraries of reagents for avian/swine flu vaccines New methods to rapidly detect the emergence of pandemic influenza strains in animals EU contribution 1,765,000 €

24. NOVAFLU More effective epidemic and pandemic vaccine strategies Optimization of vaccine strain selection Reverse genetics for high growth in cell lines Evaluation of animal models Identification of better immune correlates of protection EU contribution 1,765,000 €

25. viRgil NoE • Influenza • Hepatitis B • Hepatitis C The first-ever European Vigilance Network Addressing current and emerging antiviral drug resistance EU contribution 9,000,000 €

26. FP6 Open Call IP Post-genomic approaches to a human pandemic influenza vaccine Dead-line for proposals 16 November 2004