Transcript Influenza - WHO archives

Priority Medicines for Europe
and the World
Preparing for
Pandemic Influenza
Anna Lönnroth
European Commission
DG Research: Health Research
Chapter 6.2
Pandemic Influenza
Background paper
prepared by
David Fedson, M.D.,
in collaboration with the
WHO Global Influenza
Programme
Influenza virus
(Paul Digard, Dept Pathology, University of Cambridge)
Viral Replication
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
Antigenic drift & shift
drift
shift
(Albert Osterhaus, Erasmus University, Rotterdam, Netherlands)
1918
A U.S. Army influenza ward in Luxembourg, during the 1918 epidemic.
Photo courtesy National Museum of Health and Medicine, Armed Forces
7
Institute of Pathology,
Washington, D.C.
Deaths from infectious
diseases in USA
Deaths from infectious diseases fell in the United States during the 20th century.
8
The spike shows
the 1918 influenza pandemic, which killed more than 40 million
people, include about 500,000 Americans. Graph: CDC.
Past Influenza
Pandemics
1918
“Spanish flu”
Killed 40-50 million
H1N1
1957
“Asian flu”
killed 98.000
H2N2
1968
“Hong Kong flu”
killed 46.000
H3N2
1997
“Hong Kong”
First Human H5N1
(killing 6/18)
Man as a mixing
vessel
Re-assortant
virus
Avian virus
Avian virus
(Albert Osterhaus, Erasmus University, Rotterdam, Netherlands)
Human virus
Future Influenza
Pandemics
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 Kong
H7N7 – Netherlands
Next?
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
Pandemic
planning
Lessons learned form SARS outbreak
Identify strategies to “buy time”
Crisis management
Planning in the interpandemic period
Limitations of current
influenza vaccine
Influenza vaccine
needs to be
reformulated with
each epidemic
Prediction & public
health intervention in
advance difficult
Low vaccine uptake
although costeffective (< 20% of
expected)
Vaccine production
up-scaling capacity
insufficient & access
inequity
Available production
technology
inadequate for
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pandemic
vaccine?
Delayed vaccine
production
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
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’ 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
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
LONG 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
Industrial hurdles
Only 300 million vaccine doses are currently
produced each year (trivalent)
Upscaling challenges:
- Market insufficiency
- Market uncertainty
- Stockpiling impossible
- Regulatory & liability
issues
Incentives needed
Current capacity and resources do not
match needs for pandemic planning
Research & Development
IPR on Reverse Genetics Technology
Address liability issues
“GMO” concerns
Why Europe?
2/3 of the world’s influenza
vaccine producers are
located in Europe
EC Research
Funding
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 €
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 €
NoE
viRgil
Influenza
Hepatitis B
Hepatitis C
The first-ever
European
Vigilance
Network
EU contribution
Addressing
current and
emerging
antiviral drug
resistance
9,000,000 €
FP6 Open Call
IP
Post-genomic approaches
to a human pandemic
influenza vaccine
Dead-line for proposals
16 November 2004