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

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 Development
From the Lab to the Clinic
• Concept
• Vaccine design
• Testing

Political will Research Clinical Production Health and Access

and finance and development trials other systems and uptake

3
Vaccine Development
From 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_anticipa

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Challenges in AIDS Vaccine R&D
ISSUE WHAT IT MEANS

Scientific  HIV integrates; short window  We have to test in people

challenges  HIV hyper-variability; clades (Thai trial results)
 Immune correlates of protection  We are tackling an aggressive
are still unknown and fast-moving target
 HIV suppresses and kills cells  Success will take time
of the immune system
 Relevant animal models
are lacking
 Clinical trials are long and costly

Policy  Long-term effort requires long-term,  We need sustained political

and high-level global commitment— support
political will leading to action  We need to build private-
 Market incentives for industry sector engagement
activity lacking  We need to optimize the
 Ethical, regulatory, environment for safe,
intellectual-property issues ethical trials
 Health-systems challenges
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Social Challenges
In the Kenya Context

Community Vaccine safety

Concerns
(Kenya) Selection criteria for volunteers
Possible side effects
Approvals and clearances from government
Implications of vaccine on volunteer lifestyle
Provision of insurance
Why is Kenya participating
Patent and property rights, royalties

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Progress:
Case Study on Neutralizing Antibodies

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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 2G12
worldwide
 An AIDS vaccine will almost certainly CD4 b12
need to elicit a sufficient amount of
these broadly neutralizing antibodies gp120
2F5
gp41
4E10/Z13
This is the
neutralizing antibody
challenge
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 The Antibody Project: Protocol G

200
91
IAVI Human
Immunology
Laboratory,
London

200
50
Monogram
Biosciences
200 215 238 200

81
200

Number of donor
samples from
each site 200

1. Nearly 2,000 blood samples collected from

HIV-positive individuals around the world

2. Samples sent to Monogram Biosciences

for neutralization screening

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The Antibody Project: Identifying Prospects
3. Screening results scored using new IAVI algorithm to identify donors of interest

Blood samples collected

About 10% are donors of interest

About 1% are “elite neutralizers”

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 The Antibody Project: Closing In

IAVI Human
Immunology
Laboratory,
London

IAVI

IAVI
NAC
at Scripps

4. After data review, new samples

requested from donors of interest

5. Samples sent to IAVI Human Immunology

Laboratory

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The Antibody Project: Partners in the Hunt

IAVI Human
Immunology
Laboratory
Theraclone

HuMabs

Monogram* Rockefeller
University

IAVI
NAC
at Scripps

6. Samples sent to four partner labs for antibody

rescue—each using a different technology
*Monogram received new samples to verify neutralization screenings
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The Antibody Project: Discovery

7. Theraclone is first
to find new broadly
neutralizing antibodies

8. Antibodies
characterized

IAVI Neutralizing
Antibody Center at

AIDS Vaccine Design

and Development
Laboratory

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The Antibody Project: Next Steps

IAVI Human
Immunology
Lab

Lipoxen Pepscan
Avatar

IAVI AIDS Vaccine

ProSci Strand
Design and
Development Lab Life Sciences

Chembiotek

IAVI Neutralizing
Antibody Center
at the Scripps
Research Institute

Neutralizing Antibody
Consortium members

IAVI Innovation Fund Elevation Biotech

recipients

9. With antibodies characterized, IAVI’s

immunogen design partners take over

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The Antibody Project: The Return

Pune

Chennai

Entebbe

Nairobi IAVI-supported
Kigali
Kilifi
network
Masaka of clinical
research centers

Copperbelt
10. Ultimately, the
Lusaka
process comes full
circle with clinical
testing of vaccine
Rustenburg
candidates

Cape Town

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Questions?

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