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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