hiv vaccine clinical trials: in theory and on the ground prof. omu anzala program director kenya...
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HIV Vaccine Clinical Trials:In Theory and on the Ground
Prof. Omu Anzala
Program Director
Kenya AIDS Vaccine Initiative (KAVI)
Department of Medical Microbiology
University Of University
Kenya
18 October 2009, Paris
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Outline
• Vaccine Development—from the Lab to the Clinic• AIDS Vaccine Design• State of The Field• Clinical Trials in Kenya• Challenges in AIDS Vaccine R&D• Progress: Case Study on Neutralizing Antibodies
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Vaccine DevelopmentFrom the Lab to the Clinic
• Concept
• Vaccine design
• Testing
Political willand finance
Researchand development
Clinicaltrials
Production Health and other systems
Accessand uptake
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Vaccine DevelopmentFrom the Lab to the Clinic
• Laboratory studies
• Animal studies
• Phase I clinical trials
• Less than a hundred volunteers.
• Determine safety of the candidate vaccine.
• Phase II clinical trials
• Several hundred volunteers from low- and high-risk populations.
• Determine safety and immunogenicity in a larger population of people.
• Efficacy trials (Phase IIB/Phase III clinical trials)
• Determine efficacy of preventing HIV/AIDS (does the candidate vaccine
prevent HIV infection? and/or delay disease progression?)
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Supportive Activities for Clinical Trials
Preparations in advance of clinical trials
• Incidence studies
• Community information [Media, community reps]
• Advocacy
• Regulatory clearance
During clinical trials
• Community advisory boards inputs
• DSMB reviews
In parallel with clinical trials
• Other clinical and epi-studies, e.g.• Reference ranges• Neutralizing antibody consortium
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Vaccine Design
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State of the Field
Trials databases – up to date.
www.iavireport.org/trials-db
www.clincaltrials.gov
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Clinical Trials in Kenya
Kenya AIDS Vaccine Initiative (KAVI)
Two study sites in Nairobi:
• Phase I site at KAVI-KNH
• Phase II/III site at KAVI-Kangemi
KAVI has conducted:
• 4 Phase I HIV vaccine trials (DNA/MVA)
• One Phase II HIV vaccine trials (DNA/rAd5)
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Results of Efficacy Trials
http://www.avac.org/pdf/thai_vax_anticipating_results.EN.pdf
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WHAT IT MEANS
We have to test in people (Thai trial results)
We are tackling an aggressive and fast-moving target
Success will take time
We need sustained political support
We need to build private-sector engagement
We need to optimize the environment for safe, ethical trials
ISSUE
HIV integrates; short window
HIV hyper-variability; clades
Immune correlates of protection are still unknown
HIV suppresses and kills cellsof the immune system
Relevant animal models are lacking
Clinical trials are long and costly
Long-term effort requires long-term, high-level global commitment— leading to action
Market incentives for industry activity lacking
Ethical, regulatory,intellectual-property issues
Health-systems challenges
Scientific challenges
Policyandpolitical will
Challenges in AIDS Vaccine R&D
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Vaccine safetySelection criteria for volunteersPossible side effectsApprovals and clearances from governmentImplications of vaccine on volunteer lifestyleProvision of insuranceWhy is Kenya participatingPatent and property rights, royalties
Community Concerns(Kenya)
Social ChallengesIn the Kenya Context
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Progress: Case Study on Neutralizing Antibodies
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gp41
b12
2G12
2F54E10/Z13
CD4
gp120
This is the neutralizing antibody challenge
Most licensed vaccines work by inducing the body to produce antibodies that attack the infecting virus, neutralizing most of it and enabling the immune system to clear remaining virus before the onset of disease
In the blood of certain HIV-infected individuals, scientists have identified special antibodies that are broadly neutralizing—they neutralize many of the types of HIV in circulation worldwide
An AIDS vaccine will almost certainly need to elicit a sufficient amount of these broadly neutralizing antibodies
The Neutralizing Antibody Challenge
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1. Nearly 2,000 blood samples collected from HIV-positive individuals around the world
IAVI Human Immunology Laboratory, London
200
50
91
81
200
200
200
200238
200
215
Number of donor samples from each site
Monogram Biosciences
2. Samples sent to Monogram Biosciences for neutralization screening
The Antibody Project: Protocol G
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3. Screening results scored using new IAVI algorithm to identify donors of interest
About 1% are “elite neutralizers”
Blood samples collected
About 10% are donors of interest
The Antibody Project: Identifying Prospects
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4. After data review, new samples requested from donors of interest
IAVI
IAVINAC at Scripps
5. Samples sent to IAVI Human Immunology Laboratory
IAVI Human Immunology Laboratory, London
The Antibody Project: Closing In
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IAVI Human Immunology Laboratory
6. Samples sent to four partner labs for antibody rescue—each using a different technology
Theraclone
RockefellerUniversity
IAVINACat Scripps
HuMabs
Monogram*
*Monogram received new samples to verify neutralization screenings
The Antibody Project: Partners in the Hunt
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8. Antibodies characterized
7. Theraclone is firstto find new broadly neutralizing antibodies
IAVI Neutralizing Antibody Center at
AIDS Vaccine Design and Development Laboratory
The Antibody Project: Discovery
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IAVI AIDS Vaccine Design and Development Lab
IAVI Neutralizing Antibody Centerat the Scripps Research Institute
IAVI Human Immunology Lab
Neutralizing Antibody Consortium members
9. With antibodies characterized, IAVI’s immunogen design partners take over
StrandLife Sciences
Elevation Biotech
Chembiotek
IAVI Innovation Fund recipients
Lipoxen Pepscan
ProSci
Avatar
The Antibody Project: Next Steps
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Chennai
Pune
Kilifi
Rustenburg
Cape Town
Lusaka
Copperbelt
Kigali
Masaka
Entebbe
Nairobi
10. Ultimately, the process comes full circle with clinical testing of vaccine candidates
IAVI-supportednetworkof clinicalresearch centers
The Antibody Project: The Return
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Questions?
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