Developing for Neglected Diseases

Vaccine Technologies II Albufeira, Portugal June 5th, 2008 Douglas Holtzman, Ph.D., M.P.H. Senior Program Officer, Global Health Program Bill & Melinda Gates Foundation

1 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

2 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

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

4 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

5 Partnerships ƒ Global Alliance for Vaccines and (GAVI) ƒ Global Fund for AIDS, TB and Malaria ƒ HIV Enterprise ƒ Medicines for Malaria Venture (MMV) ƒ 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….

6 PDP-Private Sector R&D Deals: Win/Win Proposition? PDP provides • Financing PDP gets • LDC trial sites PDP • IP or low price in • Access/distribution plans LDCs Drugs • Market analysis • Rapid access and • Global health expertise • Recognition as Vaccines Joint catalyst for R&D Neglected Industry provides Industry gets Diseases • Technology candidate • IP and pricing for rich • Related know-How: countries -process engineering • Essential financing for -GCP, GLP, QC/QA small biotech firms -scale up and manufacturing Private • New technology -project management platforms with other • Financing commercial uses • Manufacturing capacity • Good will

Source: Adopted from MMV; Rockefeller Foundation

7 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

8 Pre-clinical research toward a vaccine against African trypanosomiasis

9 Objectives

ƒ To identify specific candidate that generate protective immune responses against in cattle ƒ To further test plant-based transient gene expression systems for production of vaccines appropriate for developing countries

10 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

11 Distribution of sleeping sickness in sub- Saharan Africa, 1999

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

12 Cycle of disease

Infected Systemic CNS Infection fly bite Stage I Stage II

Death

13 Antigenic shifts lead to….

VSG1 VSG2 VSGx Parasite # Time

….waves of parasitaemia

VSG = variable surface glycoprotein

14 Proof of Principle

15 Trypansome tubulin-rich regions as “Achilles Heel”

16 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 Y

S peptide delivery M system Antigenic peptide

Slide provided by Dr. Yusibov, Fraunhofer CMB

17 Mouse Experiments Show Protection

Experiment #1 Experiment #2 used Protection rate (%) Vaccine candidate Protection rate (%) Atub 1-4 60 ALMV 13 Atub 5-8 70 Atub 1-4 40 Btub 1-4 90 Atub 5-8 40 Btub 5-8 90 Btub 1-4 53 AlMV 0 Btub 5-8 100 Adjuvant 0 Btub 2 100 Btub 3 0 Btub 5 100 Btub 11 40 Tubulin (native) 27 Adjuvant 13 Atub (rec. full length) 27 Btub (rec. full length) 33 Negative control 0

Slide provided by Dr. Yusibov, Fraunhofer CMB

18 Parasitemia in cattle post challenge with T. brucei brucei

Days post challenge Groups cow -4 7 10 12 14 17 40 45

AlMV 1 - - - + + + + +

2 - + + + + + + +

3 - + + + + + + +

4 - + + + + + + +

Btub2+ Btub5 1 - - - - - + + +

2 - - - - - + + +

3 - - - - - + + +

4 - - - - - + + +

Slide provided by Dr. Yusibov, Fraunhofer CMB

19 Survival of cattle post challenge with T. brucei brucei

20 Summary

ƒ Pre-clinical program for trypanosomiasis vaccine underway - if successful, could provide a solution for an important agricultural and development issue ƒ Fraunhofer’s transient, plant-based expression system could have utility for inexpensive production of highly immunogenic recombinant vaccines for developing world

21 Partners

ƒ Dr. Vidadi Yusibov, Director of the Fraunhofer Center for Molecular Biotechnology, USA ƒ Dr. Roger Pritchard, Professor, McGill University, Canada ƒ Dr. George Lubega, Professor, Makerere University, Uganda

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