Developing Vaccines for Neglected Diseases
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Vaccine Technologies IIAlbufeira, PortugalJune 5th, 2008Douglas Holtzman, Ph.D., M.P.H.Senior Program Officer, Global Health Program
Bill & Melinda Gates Foundation
Developing Vaccines for Neglected Diseases
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Three Programs, One Goal: EquityUS Program» High school education» Public library internet access
Global Development» Financial services for the poor (e.g. microfinance)» Agricultural productivity and markets
Global Health
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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
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PrioritizationBurden of diseaseInequity of burdenLack of attentionPossibility for impact
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Disease AreasHIV (vaccines, microbicides, treatment, prevention, education)TB (drugs, vaccines, diagnostics)Malaria (drugs, vaccines, vector control, diagnostics, scale-up)PneumoniaDiarrheaNutritionMaternal HealthKinetoplastidsHelminthsHPVDengue/Japanese EncephalitisPolio
Discover, develop and deliver innovative solutions
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PartnershipsGlobal Alliance for Vaccines and Immunization (GAVI)Global Fund for AIDS, TB and MalariaHIV Vaccine EnterpriseMedicines for Malaria Venture (MMV)Malaria Vaccine Initiative (MVI)MACEPAPATH Vaccine Solutions (PVS)Aeras (TB Vaccines)Global Alliance for TB Drug Development (GATB)ACHAPGrand Challenges in Global HealthIVI/PDVIEtc….
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PDP-Private Sector R&D Deals: Win/Win Proposition?
JointR&DIndustry provides
• Technology candidate• Related know-How:
-process engineering-GCP, GLP, QC/QA-scale up and manufacturing-project management
• Financing• Manufacturing capacity
PDP gets• IP or low price in
LDCs• Rapid access • Recognition as
catalyst
Industry gets• IP and pricing for rich
countries• Essential financing for
small biotech firms• New technology
platforms with other commercial uses
• Good will
Private
Source: Adopted from MMV; Rockefeller Foundation
Drugsand
Vaccinesfor
NeglectedDiseases
PDP provides• Financing• LDC trial sites• Access/distribution plans• Market analysis• Global health expertise
PDP
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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
To identify specific candidate antigens that generate protective immune responses against Trypanosoma brucei in cattleTo further test plant-based transient gene expression systems for production of vaccines appropriate for developing countries
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African Trypanosomiasis
Parasitic disease limited to tropical Africa60M people at risk; affects all ages~40-60K annual deaths – most die unreported in the bush (~300-500K?)Resurgence of diseaseBillions of $ of lost agricultural productivityWorld’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
Infected fly bite
CNS InfectionStage II
Systemic infectionStage I
Death
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Antigenic shifts lead to….
Time
Para
site
#
….waves of parasitaemia
VSG1 VSG2 VSGx
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 VirusP1
P2
P3
CP
CP
F
P
S
T
M
P
G
C
R
K
D
A
L
I
S
Y
Antigenicpeptide
Viral gene structureElectronMicrograph
Particle-basedpeptide deliverysystem
Slide provided by Dr. Yusibov, Fraunhofer CMB
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Mouse Experiments Show Protection
0Adjuvant
0AlMV
90Btub 5-8
90Btub 1-4
70Atub 5-8
60Atub 1-4
Protection rate (%)Antigen used
0Negative control
33Btub (rec. full length)
27Atub (rec. full length)
13Adjuvant
27Tubulin (native)
40Btub 11
100Btub 5
0Btub 3
100Btub 2
100Btub 5-8
53Btub 1-4
40Atub 5-8
40Atub 1-4
13ALMV
Protection rate (%)Vaccine candidate
Experiment #1 Experiment #2
Slide provided by Dr. Yusibov, Fraunhofer CMB
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Days post challengeGroups cow -4 7 10 12 14 17 40 45
AlMV 1 - - - + + + + +
2 - + + + + + + +
3 - + + + + + + +
4 - + + + + + + +
Btub2+ Btub5 1 - - - - - + + +
2 - - - - - + + +
3 - - - - - + + +
4 - - - - - + + +
Parasitemia in cattle post challenge with T. brucei brucei
Slide provided by Dr. Yusibov, Fraunhofer CMB
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Survival of cattle post challenge withT. brucei brucei
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SummaryPre-clinical program for trypanosomiasis vaccine underway - if successful, could provide a solution for an important agricultural and development issueFraunhofer’s transient, plant-based expression system could have utility for inexpensive production of highly immunogenic recombinant vaccines for developing world
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PartnersDr. Vidadi Yusibov, Director of the Fraunhofer Center for Molecular Biotechnology, USADr. Roger Pritchard, Professor, McGill University, CanadaDr. George Lubega, Professor, MakerereUniversity, Uganda
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