Developing Vaccines for Neglected Diseases

Vaccine Technologies II Albufeira, Portugal June 5^th, 2008

Douglas Holtzman, Ph.D., M.P.H. Senior Program Officer, Global Health Program

Bill & Melinda Gates Foundation

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Three Programs, One Goal: Equity

ƒ US Program

» High school education » Public library internet access

ƒ Global Development

» Financial services for the poor (e.g. microfinance) » Agricultural productivity and markets

ƒ Global Health

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Perspective on Global Health

ƒ The vision:

To ensure that a child born in the developing world has the same chance for good health as a child born in the developed world

ƒ The goal:

Build on advances in science and technology to save lives, improve health, and reduce disease in the developing world

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Prioritization

ƒ Burden of disease ƒ Inequity of burden ƒ Lack of attention ƒ Possibility for impact

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Disease Areas

ƒ HIV (vaccines, microbicides, treatment, prevention, education) ƒ TB (drugs, vaccines, diagnostics) ƒ Malaria (drugs, vaccines, vector control, diagnostics, scale-up) ƒ Pneumonia ƒ Diarrhea ƒ Nutrition ƒ Maternal Health

Discover, develop and deliver

ƒ Kinetoplastids

innovative solutions

ƒ Helminths ƒ HPV ƒ Dengue/Japanese Encephalitis ƒ Polio

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Partnerships

ƒ Global Alliance for Vaccines and Immunization (GAVI) ƒ Global Fund for AIDS, TB and Malaria ƒ HIV Vaccine Enterprise ƒ Medicines for Malaria Venture (MMV) ƒ Malaria Vaccine Initiative (MVI) ƒ MACEPA ƒ PATH Vaccine Solutions (PVS) ƒ Aeras (TB Vaccines) ƒ Global Alliance for TB Drug Development (GATB) ƒ ACHAP ƒ Grand Challenges in Global Health ƒ IVI/PDVI ƒ Etc….

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PDP-Private Sector R&D Deals:
Win/Win Proposition?

PDP provides

• Financing

PDP gets

PDP

• LDC trial sites
• IP or low price in

• Access/distribution plans
LDCs

• Rapid access • Recognition as catalyst
Drugs and
Vaccines for
• Market analysis • Global health expertise

Joint

Neglected Diseases

R&D

Industry gets

• IP and pricing for rich countries

Industry provides

• Technology candidate • Related know-How:
-process engineering -GCP, GLP, QC/QA -scale up and manufacturing -project management
• Financing
• Essential financing for small biotech firms
• New technology platforms with other commercial uses
• Good will

Private

• Manufacturing capacity

Source: Adopted from MMV; Rockefeller Foundation

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THE GOAL
» To encourage scientific risk-taking on creative, unorthodox ideas for global health

THE INITIATIVE

» US$100 million funding initiative over 5 years » Will fund hundreds of projects based on two-page submission – next round opens September 15th

» Initial grants of $100,000 with potential for additional funding (~$1M) if promising

» Opportunity for direct engagement with the private sector

» Sign up at www.gcgh.org/explorations/ for email updates

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Pre-clinical research toward a vaccine against African trypanosomiasis

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Objectives

ƒ To identify specific candidate antigens that generate protective immune responses

against Trypanosoma brucei in cattle

ƒ To further test plant-based transient gene expression systems for production of vaccines appropriate for developing countries

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African Trypanosomiasis

ƒ Parasitic disease limited to tropical Africa ƒ 60M people at risk; affects all ages ƒ ~40-60K annual deaths – most die unreported in the bush (~300-500K?)

ƒ Resurgence of disease ƒ Billions of $ of lost agricultural productivity ƒ World’s greatest disparity disease

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Distribution of sleeping sickness in sub- Saharan Africa, 1999

WHO http://www.who.int/csr/resources/publications/CSR_ISR_2000_1tryps/en/index.html

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Cycle of disease

CNS Infection
Stage II
Infected fly bite
Systemic infection
Stage I

Death

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Antigenic shifts lead to….

VSG₁ VSG₂ VSG_x

Time

….waves of parasitaemia

VSG = variable surface glycoprotein

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Proof of Principle

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Trypansome tubulin-rich regions as “Achilles Heel”

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Technology: Alfalfa Mosaic Virus

P1 P2
P3
CP

CP

Viral gene structure
Electron

F

Micrograph

P

• C
• K

D
P

• G
• A

• T
• I

• R
• L

S

Particle-based peptide delivery system

YS
M

Antigenic peptide

Slide provided by Dr. Yusibov, Fraunhofer CMB

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Mouse Experiments Show Protection

• Experiment #1
• Experiment #2

• Antigen used
• Protection rate (%)
• Vaccine candidate
• Protection rate (%)

Atub 1-4 Atub 5-8 Btub 1-4 Btub 5-8 AlMV
60 70 90 90
0
ALMV Atub 1-4
13 40 40 53
100 100
0
Atub 5-8 Btub 1-4 Btub 5-8

• Adjuvant
• 0
• Btub 2

Btub 3

• Btub 5
• 100

40 27 13 27 33
0
Btub 11
Tubulin (native)
Adjuvant
Atub (rec. full length) Btub (rec. full length)
Negative control

Slide provided by Dr. Yusibov, Fraunhofer CMB

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Parasitemia in cattle post challenge

with T. brucei brucei

Days post challenge

Groups AlMV

• cow
• -4
• 7
• 10
• 12
• 14
• 17
• 40
• 45

12341234

--------
++++++++
++++++++
+

• -
• -
• +

+++-
++++-

+++++++

+++-
+++-

Btub2+ Btub5

• -
• -
• -
• -

• -
• -
• -
• -

• -
• -
• -
• -

Slide provided by Dr. Yusibov, Fraunhofer CMB

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Survival of cattle post challenge with

T. brucei brucei

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