Download - Preparing for Pandemic Influenza
Preparing for
Pandemic Influenza
Anna LönnrothEuropean Commission
DG Research: Health Research
Priority Medicines for Europe and the World
Chapter 6.2 Pandemic Influenza Background paper
prepared by
David Fedson, M.D., in collaboration with the
WHO Global Influenza Programme
Influenza virusInfluenza virus
(Paul Digard, Dept Pathology, University of Cambridge)
Viral ReplicationViral Replication
Annual influenza epidemics
Annual influenza epidemics
3-5 million cases of severe illness
Significant mortality among the
elderly and in developing countries
Enormous health care costs, economic
loss and work absenteeism
Current vaccines about 70 % protective
drift
shift
Antigenic drift & shiftAntigenic drift & shift
(Albert Osterhaus, Erasmus University, Rotterdam, Netherlands)
7
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.
19181918
8Deaths 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.
Deaths from infectious diseases in USA
Deaths from infectious diseases in USA
1918“Spanish flu”
Killed 40-50 million
H1N1
Past Influenza Pandemics
Past Influenza Pandemics
1957“Asian flu”
killed 98.000
H2N2
1968“Hong Kong flu”
killed 46.000
H3N2
1997“Hong Kong”
First Human H5N1
(killing 6/18)
Human virusRe-assortant virus
Avian virus Avian virus
Man as a mixing vessel
Man as a mixing vessel
(Albert Osterhaus, Erasmus University, Rotterdam, Netherlands)
Future Influenza Pandemics
Future Influenza Pandemics
Next?
Between 1997 and 2004, the H5N1 strain has gained in pathogenicity
H5N1 re-emerged in Vietnam in late 2003, killing about 70% of the infected
Possible human-human transmission of H5N1 in Thailand September 2004?
H9N2 – Hong KongH7N7 – Netherlands
Worst case scenario
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 infected
Over 1/2 billion deaths
…or worse
Lessons learned form SARS outbreak
Identify strategies to “buy time”
Crisis management
Planning in the interpandemic period
Pandemic planning
Pandemic planning
14
Influenza vaccine needs to be reformulated with each epidemic
Limitations of current influenza vaccine
Limitations of current influenza vaccine
Low vaccine uptake although cost-effective (< 20% of expected)
Prediction & public health intervention in advance difficult
Vaccine production up-scaling capacity insufficient & access inequity
Available production technology inadequate for pandemic vaccine?
Delayed vaccine production
What about treatment?
What about treatment?
1. Vaccination is by far the most efficient way to
control influenza
2. 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
Evaluate immunogenicity and safety of different monovalent, low-dose, adjuvanted ‘pandemic like’ vaccines and vaccination scheduled (avian HA)
Develop ‘antigen sparing’ strategies
Evaluate safety and effectiveness of Reverse Genetics + resolve IPR & regulatory issues
Prepare reagent libraries to speed up vaccine testing
Develop vaccine production technologies
SHORT term R&D SHORT term R&D
Explore expansion of interpandemic use and manufacturing capacity
Develop more efficient anti-viral drugs
Investigate mechanisms of drug resistance
Develop & evaluate non-medical control measures
Assess impact of common medications on clinical course of influenza-related illness
Study the public health impact of vaccination
SHORT term R&D SHORT term R&D
Develop broad spectrum vaccines that provide long lasting protection (conserved antigens)
Explore further DNA-based vaccines
Continue to develop anti-viral drugs
…underpinned by basic immunology on vaccine response, pathophysiology & host defence
Ensure availability of effective antibiotics
Evaluate long-term adverse events
LONG term R&D LONG term R&D
Industrial hurdlesIndustrial hurdles
Only 300 million vaccine doses are currently
produced each year (trivalent)
Upscaling challenges:
- Market insufficiency
- Market uncertainty
- Stockpiling impossible
- Regulatory & liability
issues
Research & Development
IPR on Reverse Genetics Technology
Address liability issues
“GMO” concerns
Incentives neededIncentives needed
Current capacity and resources do not
match needs for pandemic planning
2/3 of the world’s influenza
vaccine producers are
located in Europe
Why Europe?Why Europe?
EC Research Funding
EC Research Funding
FLUPAN 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 €EU contribution 1,765,000 €
NOVAFLU 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 €EU contribution 1,765,000 €
viRgil viRgil
The first-ever European Vigilance Network
InfluenzaHepatitis BHepatitis C
Addressing current and emerging antiviral drug resistance
EU contribution 9,000,000 €EU contribution 9,000,000 €
NoE NoE
FP6 Open Call FP6 Open Call
Post-genomic approaches Post-genomic approaches
to a human pandemic to a human pandemic
influenza vaccineinfluenza vaccine
Dead-line for proposals 16 November 2004Dead-line for proposals 16 November 2004
IP IP