tb vaccines (peg willingham)

8/7/2019 TB Vaccines (Peg Willingham)

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AERAS GLOBAL TB VACCINE FOUNDATION

By Calmette & Gurin

1908-1921

No new TB vaccine inalmost 90 years

Invention of Bacille Calmette-Gurin (BCG) Vaccine


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BCG Vaccine Efficacy BCG is one of the most widely used

vaccines in the world, yet TB remains the

second leading cause of infectious diseasedeaths

Prevents some severe forms of TB inchildren, saves 40,000 to 70,000 children a

year Fails to prevent pulmonary tuberculosis,

the most common form, and TB in adults(nearly two million people die each year)


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Tuberculosis: TB Vaccine TooDangerous for Babies With AIDS

Virus, Study SaysJuly 2, 2009 The vaccine against tuberculosis that

is routinely given to 75 percent of the worlds

infants is too risky to give to those born infectedwith the AIDS virus, says a new study publishedby the World Health Organization. Itrecommended that vaccination be delayed untilbabies can be tested.


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WHO Guidance on BCG World Health Organization (WHO)

changed guidelines in 2007

BCG is not recommended for infantsknown to be infected with HIV, due toincreased risk of disseminated BCG

disease (one percent of infants with HIVwho receive the vaccine get disseminatedBCG, 75 percent die)

Difficult to implement in practice


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Potential of a New TB Vaccine Eliminate TB as a public health

threat, in line with global targets(


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Block InitialInfection

Prevent Early

Disease

Prevent LatentInfection

PreventReactivation

Disease


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TB (all types) Incidence

0

400

800

1200

1600

2000

2010 2015 2020 2025 2030 2035 2040 2045 2050

Year

Incidencepermillion

Neonatal pre-exposure

Neonate pre-exposure + add effects

Post-exposure

Mass pre-exposure

Mass pre-exposure + post-exposure

Abu-Raddad,Sabatelli,Achterberg,Sugimoto, Longini,Dye and Halloran

All age groups

*Pre-exposure vaccine with additional effects that reduce the lifetime risk of developing disease in slow progressors byhalf to

about 2.5% and the infectiousness of the smear-positive and smear-negative cases byhalf.

*


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Aeras Global TB Vaccine FoundationMission

To develop new, more effectiveTB vaccines and ensure theiravailability to all who need them

Goals A more effective, safe and

affordable TB vaccine by 2016 Identify correlates and

surrogate markers of vaccineinduced protection

Develop second generation TBvaccines with increasedpotency and broader protection


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IndustryGlaxoSmithKline Biologicals, Belgium

Crucell, the Netherlands

Statens Serum Institute, Denmark

ImmunoBiology, United Kingdom

Wuhan Institute of Biological Products, China

Serum Institute, India

Thymed, Germany

Japan BCG Laboratory, Japan

Korean Institute of TB, Korea

Cyncron, Denmark

Immune Solutions, New Zealand

Sanofi Pasteur, France

Smittskyddsinstitutet, Sweden

Emergent BioSolutions, U.S.

Intercell, Austria

Foundations/Governments/

NGOsBill & Melinda Gates Foundation, U.S.

Ministry of Foreign Affairs of Denmark

The Netherlands Ministry of Foreign Affairs,

the Netherlands

Fogarty International Center and NIAID,

National Institutes of Health, U.S.

Research Council of Norway, Norway

Maryland Department of Business and

Economic Development, U.S.

AIDS Fondet, Denmark

Cambodian Health Committee, Cambodia

European and Developing Countries Clinical

Trials Partnership (EDCTP), European

Commission

LHL/ The Norwegian Association of Heart and

Lung Patients, Norway

Planeta Salud, Spain

Mary Lynn Richardson Fund, U.S.

Manhia Health Research Centre,

Mozambique

Medicine in Need (MEND), U.S.

Stop TB Partnership, Switzerland

TB-Alert, United Kingdom

Wellcome Trust, United Kingdom

AcademiaOxford University, United Kingdom

South African TB Vaccine Initiative (SATVI), South Africa

St. Johns Research Institute, India

Makerere University, Uganda

Kenya Medical Research Institute, Kenya

Karolinska Institute, Sweden

Wuhan University, China

Albert Einstein College of Medicine, U.S.

Arizona State University, U.S.

Aurum Institute, South Africa

Biomedical Primate Research Center, the Netherlands

Case Western Reserve University, U.S.Centre for International Health, University of Bergen, Norway

Colorado State University, U.S.

Emory University, U.S.

Food and Drug Administration, U.S.

Foundation for Innovative New Diagnostics (FIND), Switzerland

Harvard University, U.S.

International AIDS Vaccine Initiative (IAVI), U.S.

Johns Hopkins University, U.S.

KNCV Tuberculosis Foundation, the Netherlands

Leiden University Medical Center, the Netherlands

Life Science Research Israel (LSRI), Israel

Max Planck Institute for Infection Biology, GermanyNational Cancer Institute (NKI), the Netherlands

Oregon Health Sciences University, U.S.

Stanford University, U.S.

Saint Louis University., U.S.

Tuberculosis Vaccine Initiative (TBVI), Europe

Tulane University, U.S.

University of California-San Francisco, U.S.

University of California-Los Angeles, U.S.

University of Maryland, College Park, U.S.

University of Tampere, Finland

University of Wales, United Kingdom

Vanderbilt University., U.S.

Walter Reed Army Institute of Research, U.S.

Aeras Global Vaccine Development Partners

Aeras

Foundations/

Government/

NGOs

Industry

Academia


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TB Vaccine Pipeline

Additional research at the discovery/early pre-clinical level: Bhagawan Mahavir Medical Research Center; Cardiff University; EpiVax, Inc.; ImmunoBiology Ltd.; Infectious Disease ResearchInstitute; Institute de Pharamacologie, Puso; Karolinska Institute; Malaysia-Finlay Institute, NIAID; NIH; Osaka University; Shanghai H&G Biotech; Sequella; UCLA; and, Vanderbilt University.

Vaccine Candidate Pre-Clinical Phase I Phase II Phase IIb Phase III

AERAS402/Crucell Ad35Crucell N.V./Aeras

MVA85A/AERAS-485OETC/Aeras

GSK M72GSK Biologicals/Aeras

Hybrid 1 SSI IC-31SSI, TBVI, Intercell

HyVac4/AERAS-404sanofi pasteur/SSI/Intercell/Aeras

VPM 1002MaxPlanck/Vakzine ProjektManagement GmbH/TBVI

AdAg85AMcMasterUniversity

RUTIArchivel Farma, S.I.

Hybrid 1 SSI CAF01SSI

AERAS-rBCGAeras

AERAS-CapsidAeras

Other rBCG rMtbAlbert Einstein S. ofMed., Institute Pasteur, Univ. of Zaragoza, TBVI

AERAS-other virusAeras

Protein/PolysaccharidesInst. Pasteurde Lille/Inserm, Albert Einstein S. ofMed., Aeras, Karolinska Instit.


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Challenge Models ($1 million per year for 7 yrs)

TB Vaccine Development TimelineField Site Development ($2-4 million per yr, per site for 7 yrs)

2.5 Years 2 Years 4 Years

$160 Million

4 ofAeras 6 TB vaccine candidates are in clinical trials in Africa;

the others are expected to enter trials in 2010

$160 million to conduct a Phase III licensure trial of one candidate

With sufficient resources, a new TB vaccine could be ready by 2016

The Treatment Action Group estimated a $1.5 billion funding gap

for TB research for 2008 alone

1 - 2 Years 1 Year

Vaccin

eDiscovery

Pre-

ClinicalTestin

g

Phase

I

Phase

II

Phase IIb Phase III

Manufacturing ($5 million per yr for 9 yrs)

$2.5 million $4 mill ion $4 million

Licensure

$1.5 million

Costs associated with thedevelopment of allcandidates in Aeras pipeline

Costs related to thedevelopment ofone TBvaccine candidate


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Safer in HIV infected infants orothers with immune-suppression

BCG or rBCG boosted with anotherTB vaccine is much better than

either vaccine alone Constructed to over-express

antigens from each stage of the TBlife cycle

Prevent infection and reactivationutilizing prime-boost regimens

A new vaccine candidate with all ofthese properties is expected toenter clinical trials in 2010

Recombinant BCG (rBCG) - A Better BCG


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Aerosol Delivery of New TB Vaccines

Very small particles (2-4 microns)get deep into the lung, whereinfection occurs

Aerosol delivery may provide aneasy, affordable delivery mechanismthat could eliminate the need for

needles and cold chain and providesuperior protection

Spray Drying


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Example of Site Development: South Africa

Partnership with South African TuberculosisVaccine Initiative (SATVI)

Field site developed in Worcester (~120 km fromCape Town)

Infrastructure developed: State-of-the-art immunology laboratory

Highly skilled staff capable of performing theduties necessary to maintain the infrastructureand execute clinical research

Clinical and office facilities Professional Development Program

(Siyantinga- Reach for the Stars) programinitiated in 2001

Resource Center established in 2005


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Accomplishments in South Africa

South African Tuberculosis VaccineInitiative - Most advanced site for large-scale TB vaccine trials in the world

BCG randomized clinical trial of 11,680infants

Cohort studies involving more than11,500 infants and adolescents

Conducting Phase I and Phase IIstudies of 4 vaccine candidates, firstPhase IIb preliminary efficacy study of anew TB vaccine in infants in 80 years

231 staff trained since 2004, including162 female staff

Establishment of a Quality ManagementSystem and data capture mechanism


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Capacity Building Highlights at Other Sites

State-of-the-art immunology andmycobacteriology lab developed inIndia - first of its kind in the area

State-of-the-art lab and caseverification ward opened in Uganda

Quality management and datamanagement infrastructuredeveloped in India and Uganda

Professional DevelopmentPrograms

Phase I trial at Kenya site

Planned multi-country Phase II trials


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Benefits of Site Development

and Clinical Research Retain local talent and expertise

Raise awareness about TB in the community

Support and enhance local clinical research capacity

Community health and education

Infrastructure remains in the community

Leverage investment in infrastructure to use for clinicaltrials of other diseases


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Vaccine Efficacy Trials

MVA85A/AERAS-485

First efficacy trial of a newTB vaccine in infants in

more than 80 years 2,800 infants

In collaboration withSATVI, Oxford-EmergentTuberculosis Consortium

and Wellcome Trust

Additional Proof-of-Concept Studies

Planned for 2010


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Novel Approaches to Manufacturing

Building manufacturing capacity andpartnerships now to:

Reduce the cost and time tomanufacture and deliver vaccines to all

who need themProduce enough bulk doses of vaccineto meet the worlds estimated need

Work with partners in countries suchas India, China, Korea and South Africato produce, fill, finish and distributevaccines at the lowest possible price

Ensure uniformity of quality

Minimize lag time between licensure

and distribution


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Access and Availability Future access considered at every stage of vaccine

development Manufacturing

Guarantee by partners for sufficient production and affordableprices, or technology transfer

Manufactured by Aeras with partners in developing world Aeras will not consider vaccine candidates that will be costly to

manufacture on a large scale

Pricing Dual pricing for affordable distribution in resource-poor countries

Cost plus purchase from partner Aeras provides at cost

Distribution Developing world governments International organizations (GAVI, UNICEF) Developing world partners


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Aeras gratefully acknowledges the support of

the following major donors

NetherlandsMinistry of Foreign Affairs

Ministry of Foreign Affairs of Denmark

THE MARY LYNNRICHARDSON

FUND


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Thank You!

Formore information:

www.aeras.org

[email protected]

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