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A Decade of Progress in Global Immunisation


At least 300 million attacks per year. At least 1 million deaths ... Italy and the U.K. contributing the lion's share. ... South African AIDS Vaccine Initiative ... – PowerPoint PPT presentation

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Title: A Decade of Progress in Global Immunisation

A Decade of Progress in Global Immunisation
Sir Gustav Nossal Department of Pathology The
University of Melbourne Australia
IVI 10th Anniversary International
Symposium, Seoul, Korea, April 2, 2008
A Decade of the International Vaccine Institute
  • Development of new vaccines has accelerated
  • Dynamic new funding sources for global
  • The IVIs Special Niche

Critical analyses of disease burden.
Cost-benefit analyses and priority setting.
Early clinical trials of safety and
immunogenicity. Controlled trials of vaccine
efficacy. Large scale demonstration projects.
What Has Allowed IVI To Be So Successful?
  • Dynamic Leadership
  • Skill and Experience of the Staff
  • Extraordinary Networking
  • Extensive International Collaboration
  • Outstanding Support from Korean Government
  • Major Gates Foundation Funding

How To Thrive Without The Big Three?
  • Concentrate on the less glamorous and more
    neglected killers

Diarrheal Diseases Acute Respiratory
Infections Mosquito-Borne Viral Diseases
  • Concentrate Laboratory Studies on Pivotal Areas

Mucosal Immunity Innate Immunity Better
Where Does The IVI Fit In?
  • Best conceptualized as part of the United Nations
    new thrust to meet the Millennium Development
  • Extreme poverty can be eradicated. Improvement in
    health outcomes will be central to that.
  • This paper will argue that the world can afford
    to make a real impact on the communicable
    diseases which so unfairly still affect the
    poorer countries.

  • In July, 2005, the G8 group of nations committed
    themselves to a new global imperativeget rid
    of extreme poverty in the world, especially in
  • What is needed is a new Marshall Plan.

The Moral Imperative of Poverty Reduction
Our policy is directed not against any country
or doctrine but against hunger, poverty,
desperation and chaos. Theres no doubt in my
mind that the whole world hangs in the
balance. U.S. Secretary of State George C.
Marshall, 1948, commenting on the Marshall Plan
for the reconstruction of Europe which cost USA
4 of GDP for some years (todays equivalent 500
billion/year). Make Poverty History Bono and
Bob Geldof, July 2005
The Moral Imperative of Health
  • Important from a humanitarian point of view
  • Important from an educational point of view
  • Important from an economic point of view
  • A virtuous circle unites health, education and
    economic growth
  • 41 life-saving interventions would cost 40 per
    person per year and save 8 million lives per
  • Economic benefit would be 6 for every dollar

The Moral Imperative of Health (continued)
  • There is absolutely no excuse for us to live on
    a planet where, at 10 cents per 100, millions of
    lives could be saved every year. Its hard to
    understand why we kill people, but absolutely
    unthinkable how we let millions of people die
    when we stand by without understanding what is in
    our own interest and moral obligation.
  • Jeffrey D. Sachs, Earth Institute, Columbia
    University, 2003.
  • 2007 World GDP 51 trillion 10 cents/100 51
    billion2007 U.S. Health Expenditure 2.2
    trillion2007 World Health Expenditure 5
    trillion 1 50 billion

The Moral Imperative of Communicable Diseases
Within health, the aid priorities should be
  • Infectious Diseases
  • Nutrition, especially micronutrients
  • Antenatal and Obstetric Care
  • Birth spacing
  • Diabetes

Health Progress is Possible
  • Deaths in children under 5 a record low in 2006,
    9.7 million versus 13 million in 1990.
  • Sub-Saharan Africa 4.8 million, South Asia 3.1
  • Among preventable deaths

Pneumonia 1.8 million Diarrhoea 1.6
million Malaria 780 thousand Measles 390
thousand AIDS 290 thousand
Global Fund to Fight AIDS, TB and Malaria
  • In first 5 years of programme, U.S. 8.4 billion
    pledged to 136 countries.
  • 770,000 patients on HAART.
  • 9.4 million people given HIV testing/counselling.
  • 2 million people on TB chemotherapy.
  • 18 million insectide-impregnated bednets
  • 23 million malaria treatments given.

Presidents Emergency Plan for AIDS Relief
  • President Bush requests 5.8 billion for F.Y.
  • 4.2 billion goes to HAART for 15 focus
  • Funds also provided to Global Fund and malaria
  • Aim is to treat 2 million people in 2008
    combining both funds.
  • Goal for G8 and UN By 2010, 100 coverage of
    AIDS patients.

  • 2 billion people infected
  • 9 million new cases per year
  • 2 million deaths per year
  • DOTS works reasonably well resistance to first
    line drugs a problem MDR XDR

Polio Eradication is Still Problematic
  • 4 Polio endemic countries
  • (Cases to date 2008)

India (132) Nigeria (46) Afghanistan (4) Pakistan
  • 5 Importation countries remain of 27 re-infected.
  • Somalia now polio free last case March 25, 2007.
  • Finishing the job of polio eradication is our
    best buy.
  • We must do it

Margaret Chan
  • At least 300 million attacks per year
  • At least 1 million deaths
  • Resistance to drugs Anopheles resistance to
  • Insecticide impregnated bed nets
  • New drugs Medicines for Malaria 5
    artemisinine derivatives

The Moral Imperative of Acute Respiratory
Diseases and Meningitis
  • 7 to 11-valent pneumococcal conjugate vaccines
    work well but are expensive
  • Genome mining to find one or more common protein
    vaccines would help greatly
  • Haemophilus influenza B and Neisseria
    meningitidis C conjugate vaccines have been very
  • N. meningitidis A conjugate is being trialled for
  • N. meningitidis B and non-typable Haemophilus
    require more work

The Moral Imperative of Diarrhoeal Diseases
  • Two rotavirus vaccines have been registered and
    more are in the pipeline
  • 600,000 deaths per year
  • Pre-clinical vaccines for shigellosis look good
    clinical research is slow
  • Good vaccines against cholera and typhoid exist
    but are not being used
  • Progress with enterotoxigenic E. coli vaccine is
    fairly good

The Moral Imperative of Vaccines Which Prevent
Viral Causes of Cancer
  • Increased use of hepatitis B vaccine through GAVI
    is heartening
  • Some research progress towards a hepatitis C
  • The human papilloma virus vaccine has been
    brilliantly successful
  • For the second generation, more HPV genotypes
    will have to be included
  • Plans for a Helicobacter pylori vaccine are on
    hold. Peptic ulcer disease and gastric cancer are
    very important

Other Vaccines of the Future
  • Bird Flu
  • SARS
  • Dengue
  • Anti-terrorism
  • Schistosomiasis
  • Leishmaniasis
  • Hookworm
  • Group A streptococci
  • and many many more !

Progess of the GAVI Alliance 20002007
  • 36.8 million extra children received standard
  • 176 million children received any or all of
    hepatitis B, Hib and yellow fever vaccines.
  • Measles deaths reduced by 60 (aiming for 90 by
  • Estimated 2.9 million deaths prevented.
  • Bill Gates re his 1.5 billion donation My best
    investment ever.

GAVI Alliance Challenges
  • 28 million children each year still not
  • Still 2.5 million vaccine-preventable deaths each
  • Need 10 to 15 billion extra over next ten years.

International Finance FacilityImmunisation
  • Bonds issued through the international capital
    markets guaranteeing large, immediately available
    sums and are redeemed via legally binding pledges
    from governments of donor countries.
  • On 14 November, 2006 IFFIm placed US1 million 5
    year bonds at 5.2. Investors included central
    banks, major funds but also Mums and Dads.
  • Over the next 10 years, IFFIm plans to raise US4
    billion for the GAVI Alliance.
  • Donor countries are France, Italy, Norway, South
    Africa, Spain, Sweden and the U.K.

Advanced Market Commitments (AMCS) for Vaccines
  • A new mechanism for development and subsidised
    purchase of priority vaccines, including ones not
    yet invented.
  • On 9 February 2007, Streptococcus pneumoniae was
    chosen as the first target as it kills 1.6
    million people annually.
  • US 1.5 billion pledged with Italy and the U.K.
    contributing the lions share.
  • AMCS will fund research, support development,
    provide funds for a sustainable supply and
    negotiate a reasonable price.

Progress with Specific Vaccines African
  • WHOPATH Meningitis Vaccine Initiative on track
    using monovalent Mening A conjugate.
  • Production is by Serum Institute of India, Pune,
    in association with 2 CROs for technology
  • 8 June 2007 600 12-23 month old children I Mali
    and The Gambia make 20 times more antibody than
    with unconjugated vaccine.
  • Dell Foundation to fund demonstration study
    Single dose all 1-29 year olds in Burkina Faso in
  • 400 million will be required to immunize 350
    million people in 20 other countries.

Progress with Specific Vaccines Malaria
  • GSK sporozoite vaccine RTS, S with AS02D adjuvant
    shown to be safe and immunogenic in children aged
    3 to 5 in Mozambique.
  • Per cent efficacy and duration of protection
    remain problems with this vaccine.
  • Two studies of blood stage antigen AMA-1 are in
    Phase I clinical trial.
  • Steve Hoffmans live, attenuated, mosquito
    salivary gland-derived vaccine (Sanaria) 90
    effective in human volunteers for 4 years.
    Clinical trials are planned for 2008.

Progress with Specific Vaccines Tuberculosis
  • September 2007 Aeras Tuberculosis Vaccine
    Foundation receives 200 million from Gates
  • Strategies include new BCG strains with genes for
    selected soluble antigens as well as novel
    recombinant proteins with novel adjuvants and
    also primeboost regimens using adenovirus 35.
    Promising antigens include ESAT6, Ag85B, TB 10.4
    and HSP90.
  • 6 Phase I studies have started or are about to
    start. Latest is Peter Andersen Ag85B and TB10.4
    in IC31 adjuvant from Intercell.
  • 2 Phase 3 trials hoped for by late 2010.

Progress with Specific Vaccines HIV / AIDS (1)
Progress with Specific Vaccines HIV / AIDS (2)
  • About 30 candidates in early clinical trials.
  • 2 candidates in efficacy trials

Sanofi-Pasteur canarypox vector with HIV
inserts, boost with Vaxgen gp120 (16,000 persons
in Thailand). Merck on September 21, 2007,
STOPPED its trial of adenovirus serotype 5 with
gag, pol and nef expressed because of failure to
prevent infection or to lower set point.
Progress with Specific Vaccines HIV / AIDS (3)
Some Promising Strategies
  • Mimic trimeric env. structure
  • Stabilize or mimic intermediate (cross-linked
    env-CD4) in HIV binding process, e.g. gp120-CD4
    complexes or analogues.
  • Mimotopes of those epitopes to which broadly
    neutralizing monoclonal antibodies bind.
  • New adjuvants, new prime-boost regimens.
  • Shorten clinical trials by looking for what
    reduces the set point of virus load.
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