Developing Vaccines for Neglected Diseases

Transcription

1 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 1

2 Three Programs, One Goal: Equity US Program» High school education» Public library internet access Global Development» Financial services for the poor (e.g. microfinance)» Agricultural productivity and markets Global Health 2

3 Perspective on Global Health 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 The goal: Build on advances in science and technology to save lives, improve health, and reduce disease in the developing world 3

4 Prioritization Burden of disease Inequity of burden Lack of attention Possibility for impact 4

5 Disease Areas HIV (vaccines, microbicides, treatment, prevention, education) TB (drugs, vaccines, diagnostics) Malaria (drugs, vaccines, vector control, diagnostics, scale-up) Pneumonia Diarrhea Nutrition Maternal Health Kinetoplastids Helminths HPV Dengue/Japanese Encephalitis Polio Discover, develop and deliver innovative solutions 5

6 Partnerships Global Alliance for Vaccines and Immunization (GAVI) Global Fund for AIDS, TB and Malaria HIV Vaccine Enterprise Medicines for Malaria Venture (MMV) Malaria Vaccine Initiative (MVI) MACEPA PATH Vaccine Solutions (PVS) Aeras (TB Vaccines) Global Alliance for TB Drug Development (GATB) ACHAP Grand Challenges in Global Health IVI/PDVI Etc. 6

7 PDP-Private Sector R&D Deals: Win/Win Proposition? PDP provides Financing LDC trial sites Access/distribution plans Market analysis Global health expertise Industry provides Technology candidate Related know-how: -process engineering -GCP, GLP, QC/QA -scale up and manufacturing -project management Financing Manufacturing capacity PDP Joint R&D Private PDP gets IP or low price in LDCs Rapid access Recognition as catalyst Source: Adopted from MMV; Rockefeller Foundation Industry gets IP and pricing for rich countries Essential financing for small biotech firms New technology platforms with other commercial uses Good will Drugs and Vaccines for Neglected Diseases 7

8 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 for updates 8

9 Pre-clinical research toward a vaccine against African trypanosomiasis 9

10 Objectives To identify specific candidate antigens that generate protective immune responses against Trypanosoma brucei in cattle To further test plant-based transient gene expression systems for production of vaccines appropriate for developing countries 10

11 African Trypanosomiasis Parasitic disease limited to tropical Africa 60M people at risk; affects all ages ~40-60K annual deaths most die unreported in the bush (~ K?) Resurgence of disease Billions of $ of lost agricultural productivity World s greatest disparity disease 11

12 Distribution of sleeping sickness in sub- Saharan Africa, 1999 WHO 12

13 Cycle of disease Infected fly bite Systemic infection Stage I CNS Infection Stage II Death 13

14 Antigenic shifts lead to. VSG 1 VSG 2 VSG x Parasite # Time.waves of parasitaemia VSG = variable surface glycoprotein 14

15 Proof of Principle 15

16 Trypansome tubulin-rich regions as Achilles Heel 16

17 M S C P G T R P F K L D A I Y S Technology: Alfalfa Mosaic Virus P1 P2 P3 CP CP Electron Micrograph Viral gene structure Particle-based peptide delivery system Antigenic peptide Slide provided by Dr. Yusibov, Fraunhofer CMB 17

18 Mouse Experiments Show Protection Experiment #1 Experiment #2 Antigen used Protection rate (%) Vaccine candidate Protection rate (%) Atub ALMV 13 Atub Atub Btub Atub Btub Btub AlMV 0 Btub Adjuvant 0 Btub Btub 3 0 Btub Btub 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

19 Parasitemia in cattle post challenge with T. brucei brucei Days post challenge Groups cow AlMV Btub2+ Btub Slide provided by Dr. Yusibov, Fraunhofer CMB 19

20 Survival of cattle post challenge with T. brucei brucei 20

21 Summary Pre-clinical program for trypanosomiasis vaccine underway - if successful, could provide a solution for an important agricultural and development issue Fraunhofer s transient, plant-based expression system could have utility for inexpensive production of highly immunogenic recombinant vaccines for developing world 21

22 Partners Dr. Vidadi Yusibov, Director of the Fraunhofer Center for Molecular Biotechnology, USA Dr. Roger Pritchard, Professor, McGill University, Canada Dr. George Lubega, Professor, Makerere University, Uganda 22