Developing Vaccines 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 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 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 Prioritization Burden of disease Inequity of burden Lack of attention Possibility for impact
4 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 Discover, develop and deliver Kinetoplastids innovative solutions Helminths HPV Dengue/Japanese Encephalitis Polio
5 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 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
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 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 (~300-500K?) Resurgence of disease Billions of $ of lost agricultural productivity 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 infection 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 Antigen 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
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 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
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