Developing Vaccines for Neglected Diseases

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 1Three 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 2Perspective 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 3Prioritization ƒ Burden of disease ƒ Inequity of burden ƒ Lack of attention ƒ Possibility for impact 4Disease 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 5Partnerships 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…. 6PDP-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 7THE 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 <a href="/goto?url=http://www.gcgh.org/explorations/" target="_blank">www.gcgh.org/explorations/ </a>for email updates 8Pre-clinical research toward a vaccine against African trypanosomiasis 9Objectives 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 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 <a href="/goto?url=http://www.who.int/csr/resources/publications/CSR_ISR_2000_1tryps/en/index.html" target="_blank">WHO http://www.who.int/csr/resources/publications/CSR_ISR_2000_1tryps/en/index.html </a>12 Cycle of disease CNS Infection Stage II Infected fly bite Systemic infection Stage I Death 13 Antigenic shifts lead to…. VSG1 VSG2 VSGx 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 FMicrograph P<ul style="display: flex;"><li style="flex:1">C</li><li style="flex:1">K</li></ul>D P<ul style="display: flex;"><li style="flex:1">G</li><li style="flex:1">A</li></ul><ul style="display: flex;"><li style="flex:1">T</li><li style="flex:1">I</li></ul><ul style="display: flex;"><li style="flex:1">R</li><li style="flex:1">L</li></ul>SParticle-based peptide delivery system YS MAntigenic peptide Slide provided by Dr. Yusibov, Fraunhofer CMB 17 Mouse Experiments Show Protection <ul style="display: flex;"><li style="flex:1">Experiment #1 </li><li style="flex:1">Experiment #2 </li></ul><ul style="display: flex;"><li style="flex:1">Antigen used </li><li style="flex:1">Protection rate (%) </li><li style="flex:1">Vaccine candidate </li><li style="flex:1">Protection rate (%) </li></ul>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 <ul style="display: flex;"><li style="flex:1">Adjuvant </li><li style="flex:1">0</li><li style="flex:1">Btub 2 </li></ul>Btub 3 <ul style="display: flex;"><li style="flex:1">Btub 5 </li><li style="flex:1">100 </li></ul>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 18 Parasitemia in cattle post challenge with T. brucei brucei Days post challenge Groups AlMV <ul style="display: flex;"><li style="flex:1">cow </li><li style="flex:1">-4 </li><li style="flex:1">7</li><li style="flex:1">10 </li><li style="flex:1">12 </li><li style="flex:1">14 </li><li style="flex:1">17 </li><li style="flex:1">40 </li><li style="flex:1">45 </li></ul>12341234-------- ++++++++ ++++++++ +<ul style="display: flex;"><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">+</li></ul>+++- ++++-++++++++++- +++-Btub2+ Btub5 <ul style="display: flex;"><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">-</li></ul><ul style="display: flex;"><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">-</li></ul><ul style="display: flex;"><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">-</li><li style="flex:1">-</li></ul>Slide provided by Dr. Yusibov, Fraunhofer CMB 19 Survival of cattle post challenge with T. brucei brucei 20

Developing Vaccines for Neglected Diseases

Details

Download

Copyright

We respect the copyrights and intellectual property rights of all users. All uploaded documents are either original works of the uploader or authorized works of the rightful owners.

Support