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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